Background The quality and yield of cashmere fibre are closely related to the differentiation and development of secondary hair follicles in the skin of cashmere goats.The higher the density of secondary hair follicle...Background The quality and yield of cashmere fibre are closely related to the differentiation and development of secondary hair follicles in the skin of cashmere goats.The higher the density of secondary hair follicles,the higher the quality and yield of cashmere from the fleece.Development of secondary hair follicles commences in the embryonic stage of life and is completed 6 months after birth.Preliminary experimental results from our laboratory showed that melatonin(MT)treatment of goat kids after their birth could increase the density of secondary hair follicles and,thus,improve the subsequent yield and quality of cashmere.These changes in the secondary hair follicles resulted from increases in levels of antioxidant and expression of anti-apoptotic protein,and from a reduction in apoptosis.The present study was conducted to explore the molecular mechanism of MT-induced secondary hair follicle differentiation and development by using whole-genome analysis.Results MT had no adverse effect on the growth performance of cashmere kids but significantly improved the character of the secondary hair follicles and the quality of cashmere,and this dominant effect continued to the second year.Melatonin promotes the proliferation of secondary hair follicle cells at an early age.The formation of secondary hair follicles in the MT group was earlier than that in the control group in the second year.The genome-wide data results involved KEGG analysis of 1044 DEmRNAs,91 DElncRNAs,1054 DEcircRNAs,and 61 DEmiRNAs which revealed that the mitogen-activated protein kinase(MAPK)signaling pathway is involved in the development of secondary hair follicles,with key genes(FGF2,FGF21,FGFR3,MAPK3(ERK1))being up-regulated and expressed.We also found that the circMPP5 could sponged miR-211 and regulate the expression of MAPK3.Conclusions We conclude that MT achieves its effects by regulating the MAPK pathway through the circMPP5 sponged the miR-211,regulating the expression of MAPK3,to induce the differentiation and proliferation of secondary hair follicle cells.In addition there is up-regulation of expression of the anti-apoptotic protein causing reduced apoptosis of hair follicle cells.Collectively,these events increase the numbers of secondary hair follicles,thus improving the production of cashmere from these goats.展开更多
Objective To investigate the distribution and dynamic changes of both Wnt signaling molecules and CK15 throughoutthe three phases of the follicular cycle,and to explore the relationship between Wnt/β-catenin signalin...Objective To investigate the distribution and dynamic changes of both Wnt signaling molecules and CK15 throughoutthe three phases of the follicular cycle,and to explore the relationship between Wnt/β-catenin signaling and CK15 in rat whisker hair follicle(HF)growth cycles.Methods Hematoxylin-Eosin(HE)and immunofluorescence stains were used to characterize the expression patterns,including sites and levels of some representative proteins of both canonical and non-canonical Wnt signaling molecules,as well as HF epithelial stem cell marker CK15.Results The expression patterns of bothβ-catenin and Wnt5a were correlated with that of CK15.CK15 was only expressed in anagen.In catagen,β-catenin showed a massive depletion while Wnt5a noticeably increased.In telogen,high level expression ofβ-catenin and low level of Wnt5a were detected.Wnt10b and TCF3 were detected during the entire HF growth cycle.Conclusion These results suggest that Wnt5a is associated with the transition of anagen-catagen phase,accompanied by broad deletion ofβ-catenin and loss of CK15.WntlOb is important for the maintenance of HF activity and is related to the telogenanagen transition.展开更多
With the completion of the draft assembly of the giant panda genome sequence,RNA sequencing technology has been widely used in genetic research on giant pandas.We used RNA-seq to examine black and white hair follicle ...With the completion of the draft assembly of the giant panda genome sequence,RNA sequencing technology has been widely used in genetic research on giant pandas.We used RNA-seq to examine black and white hair follicle samples from adult pandas.By comparison with the giant panda genome,75963 SNP loci were labeled,2426 differentially expressed genes(DEGs)were identified,and 2029 new genes were discovered,among which 631 were functionally annotated.A cluster analysis of the DEGs showed that they were mainly related to the Wnt signaling pathway,ECM–receptor interaction,the p53 signaling pathway,and ribosome processing.The enrichment results showed that there were significant differences in the regulatory networks of hair follicles with different colors during the transitional stage of hair follicle resting growth,which may play a regulatory role in melanin synthesis during growth.In conclusion,our results provide new insights and more data support for research on the color formation in giant pandas.展开更多
Hair follicle stem cells(HFSCs)in the bulge are a multipotent adult stem cell population.They can periodically give rise to new HFs and even regenerate the epidermis and sebaceous glands during wound healing.An increa...Hair follicle stem cells(HFSCs)in the bulge are a multipotent adult stem cell population.They can periodically give rise to new HFs and even regenerate the epidermis and sebaceous glands during wound healing.An increasing number of biomarkers have been used to isolate,label,and trace HFSCs in recent years.Considering more detailed data from single-cell transcriptomics technology,we mainly focus on the important HFSC molecular markers and their regulatory roles in this review.展开更多
Background:Sweat glands(SGs)and hair follicles(HFs)are two important cutaneous appendages that play crucial roles in homeostatic maintenance and thermoregulation,and their interaction is involved in wound healing.SGs ...Background:Sweat glands(SGs)and hair follicles(HFs)are two important cutaneous appendages that play crucial roles in homeostatic maintenance and thermoregulation,and their interaction is involved in wound healing.SGs can be regenerated from mesenchymal stem cell-laden 3D bioprinted scaffolds,based on our previous studies,whereas regeneration of HFs could not be achieved in the same model.Due to the lack of an in vitro model,the underlying molecular mechanism of the interaction between SGs and HFs in regeneration could not be fully understood.The purpose of the present study was to establish an in vitro model of skin constructs with SGs and HFs and explore the interaction between these two appendages in regeneration.Methods:To investigate the interaction effects between SGs and HFs during their regeneration processes,a combined model was created by seeding HF spheroids on 3D printed SG scaffolds.The interaction between SG scaffolds and HF spheroids was detected using RNA expression and immunofluorescence staining.The effects of microenvironmental cues on SG and HF regeneration were analysed by altering seed cell types and plantar dermis homogenate in the scaffold.Results:According to this model,we overcame the difficulties in simultaneously inducing SG and HF regeneration and explored the interaction effects between SG scaffolds and HF spheroids.Surprisingly,HF spheroids promoted both SG and HF differentiation in SG scaffolds,while SG scaffolds promoted SG differentiation but had little effect on HF potency in HF spheroids.Specifically,microenvironmental factors(plantar dermis homogenate)in SG scaffolds effectively promoted SG and HF genesis in HF spheroids,no matter what the seed cell type in SG scaffolds was,and the promotion effects were persistent.Conclusions:Our approach elucidated a new model for SG and HF formation in vitro and provided an applicable platform to investigate the interaction between SGs and HFs in vitro.This platform might facilitate 3D skin constructs with multiple appendages and unveil the spatiotemporal molecular program of multiple appendage regeneration.展开更多
Clinical applications of cell therapy and tissue regeneration under different conditions need a multiplicity of adult stem cell sources.Up to date,little is available on the comparative isolation,characterization,prol...Clinical applications of cell therapy and tissue regeneration under different conditions need a multiplicity of adult stem cell sources.Up to date,little is available on the comparative isolation,characterization,proliferation,rapid amplification,and osteogenic/adipogenic differentiation of rat mesenchymal stem cells(MSCs)isolated from living bulge cells of the hair follicle(HF)and bone marrow(BM)from the same animal.This work hopes to use HF-MSCs as an additional adult stem cell source for research and application.After reaching 80%confluence,the cell counting,viability%,and yields of HF-MSCs and BM-MSCs were nearly similar.The viability%was 91.41±2.98 and 93.11±3.06 while the cells yield of initial seeding was 33.15±2.76 and 34.22±3.99 and of second passage was 28.76±1.01 and 29.56±3.11 for HF-MSCs and BM-MSCs respectively.Clusters of differentiation(CDs)analysis revealed that HF-MSCs were positively expressed CD34,CD73 and CD200 and negatively expressed CD45.BM-MSCs were positively expressed CD73 and CD200 and negatively expressed of CD34 and CD45.The proliferation of HFMSCs and BM-MSCs was determined by means of incorporation of Brd-U,population doubling time(PDT)assays and the quantity of formazan release.The percentage of Brd-U positive cells and PDT were relatively similar in both types of cells.The proliferation,as expressed by the quantity of formazan assay in confluent cells,revealed that the quantity of release by BM-MSCs was slightly higher than HF-MSCs.Adipogenic differentiated BM-MSCs showed moderate accumulation of oil red-O stained lipid droplets when compared to that of HF-MSCs which exhibited high stain.The total lipid concentration was significantly higher in adipogenic differentiated HF-MSCs than BMMSCs(P<0.05).It was found that activity of bone alkaline phosphatase and calcium concentration were significantly higher(P<0.01 and P<0.05 respectively)in osteogenic differentiated BM-MSCs than that of HF-MSCs.The present findings demonstrate that the HF-MSCs are very similar in most tested characteristics to BM-MSCs with the exception of differentiation.Additionally;no issues have been reported during the collection of HF-MSCs.Therefore,the HF may represent a suitable and accessible source for adult stem cells and can be considered an ideal cell source for adipogenesis research.展开更多
Hair follicles are easily accessible skin appendages that protect against cold and potential injuries.Hair follicles contain various pools of stem cells,such as epithelial,melanocyte,and mesenchymal stem cells(MSCs)th...Hair follicles are easily accessible skin appendages that protect against cold and potential injuries.Hair follicles contain various pools of stem cells,such as epithelial,melanocyte,and mesenchymal stem cells(MSCs)that continuously self-renew,differentiate,regulate hair growth,and maintain skin homeostasis.Recently,MSCs derived from the dermal papilla or dermal sheath of the human hair follicle have received attention because of their accessibility and broad differentiation potential.In this review,we describe the applications of human hair follicle-derived MSCs(hHF-MSCs)in tissue engineering and regenerative medicine.We have described protocols for isolating hHF-MSCs from human hair follicles and their culture condition in detail.We also summarize strategies for maintaining hHF-MSCs in a highly proliferative but undifferentiated state after repeated in vitro passages,including supplementation of growth factors,3D suspension culture technology,and 3D aggregates of MSCs.In addition,we report the potential of hHF-MSCs in obtaining induced smooth muscle cells and tissue-engineered blood vessels,regenerated hair follicles,induced red blood cells,and induced pluripotent stem cells.In summary,the abundance,convenient accessibility,and broad differentiation potential make hHF-MSCs an ideal seed cell source of regenerative medical and cell therapy.展开更多
Skin contains various populations of stem cells (SCs). Among these are hair follicle stem cells (HFSCs) in the bulge region. The behavior of HFSCs deserves to be widely studied due to the benefits to be derived from t...Skin contains various populations of stem cells (SCs). Among these are hair follicle stem cells (HFSCs) in the bulge region. The behavior of HFSCs deserves to be widely studied due to the benefits to be derived from their identification, isolation, and amplification. Skin samples of newborn mice (n = 32) and human adults (n = 10) were used, and the bulge region was isolated and cultured. The isolation and characterization of cells were conducted through immunocytochemistry and immunofluorescence, using mainly CD34 and CD200 monoclonal antibodies. Initially, cells grew slowly from the explant around the bulge region, accruing cells with different morphology in both mouse and human, latter being mostly polygonal;the mouse cells reaching confluence faster (5 to 7 days) than the human (12 to 15 days). It was possible to isolate into subcultures cells with small size (10 - 13 μm diameter), round-shape, scant cytoplasm, central prominent nucleus and with nucleolus, which formed colonies, maintaining their phenotype in a high proportion (77% - 83% and 91% in mouse and human, respectively), without showing changes in their morphology during almost 7 months in the mouse cells, and a month and a half in the human. These results demonstrate that the selection, the isolation, and the conditioned mediums allowed population increases of bulge cells and indicate that cultured cells may retain their sternness in that they maintained their phenotypic characteristics, expressed specific markers for SCs, and showed a high proliferative capacity for long periods. Hair follicles, in mice and humans, are important repositories of multipotent stem cells, due to their tendency to differentiate into keratinocytes. Human HFSCs, obtained by depilation, preserve their potential for proliferation and prove to be easily accessible. This suggests that the bulge cells may present an alternative source of autologous stem cells for tissue engineering and regenerative medicine.展开更多
Background:Cisplatin is a chemotherapeutic agent commonly used clinically for the treatment of various human cancers.Patients often reduce the use of cisplatin due to its side effects,which in turn affects its treatme...Background:Cisplatin is a chemotherapeutic agent commonly used clinically for the treatment of various human cancers.Patients often reduce the use of cisplatin due to its side effects,which in turn affects its treatment.This study explored the mechanism of action of safflower extract as an adjuvant traditional Chinese medicine for chemotherapy.Methods:Primary human follicle dermal papilla cells(HFDPCs)were used as target cells for cisplatininduced damage to hair cells.Western blotting was used to investigate the molecular targets of cisplatin and safflower extract in causing HFDPCs damage.Cell survival and cell cycle were analyzed by mitochondrial staining reagent WST-1 and propidium iodide.Results:Cisplatin could reduce the viability of HFDPCs without causing cell death.Cisplatin increased the level of phospho-Rad17 in HFDPCs and activated the Chk1/Cdc25C signaling to reduce the expression of Cdc2 protein,thereby arresting the cells in the G2/M phase.The combination of safflower extract and the flavonoids could effectively inhibit the signal transduction of Rad17/Chk1/Cdc25 in cisplatin-treated cells and reduce the cell population in the G2/M phase.Finally,we also confirmed that safflower extract could effectively inhibit the damage to HFDPCs caused by cisplatin,mainly at the level of reducing the DNA damage caused by cisplatin.Conclusions:Safflower extract can be used as an adjuvant Chinese medicine for chemotherapy to reduce the damage caused by chemotherapy to normal hair follicle cells.展开更多
Hair loss affects millions of people at some time in their life,and safe and efficient treatments for hair loss are a significant unmet medical need.We report that topical delivery of quercetin(Que)stimulates resting ...Hair loss affects millions of people at some time in their life,and safe and efficient treatments for hair loss are a significant unmet medical need.We report that topical delivery of quercetin(Que)stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice.We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1αin endothelial cells.Skin administration of a HIF-1αagonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que.Together,these findings provide a molecular understanding for the efficacy of Que in hair regrowth,which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine,and suggest a route of pharmacological intervention that may promote hair regrowth.展开更多
Hair follicle stem cells(HFSCs)reside in the bulge region of the outer root sheath of the hair follicle.They are considered slow-cycling cells that are endowed with multilineage differentiation potential and superior ...Hair follicle stem cells(HFSCs)reside in the bulge region of the outer root sheath of the hair follicle.They are considered slow-cycling cells that are endowed with multilineage differentiation potential and superior proliferative capacity.The normal morphology and periodic growth of HFSCs play a significant role in normal skin functions,wound repair and skin regeneration.The HFSCs involved in these pathophysiological processes are regulated by a series of cell signal transduction pathways,such as lymphoid enhancer factor/T-cell factor,Wnt/β-catenin,transforming growth factor-β/bone morphogenetic protein,Notch and Hedgehog.The mechanisms of the interactions among these signaling pathways and their regulatory effects on HFSCs have been previously studied,but many mechanisms are still unclear.This article reviews the regulation of hair follicles,HFSCs and related signaling pathways,with the aims of summarizing previous research results,revealing the regulatory mechanisms of HFSC proliferation and differentiation and providing important references and new ideas for treating clinical diseases.展开更多
Hair follicles(HFs)undergo cycles of degeneration(catagen),rest(telogen),and regeneration(anagen)phases.Anagen begins when the hair follicle stem cells(HFSCs)obtain sufficient activation cues to overcome suppressive s...Hair follicles(HFs)undergo cycles of degeneration(catagen),rest(telogen),and regeneration(anagen)phases.Anagen begins when the hair follicle stem cells(HFSCs)obtain sufficient activation cues to overcome suppressive signals,mainly the BMP pathway,from their niche cells.Here,we unveil that mTOR complex 1(mTORC1)signaling is activated in HFSCs,which coincides with the HFSC activation at the telogen-to-anagen transition.By using both an inducible conditional gene targeting strategy and a pharmacological inhibition method to ablate or inhibit mTOR signaling in adult skin epithelium before anagen initiation,we demonstrate that HFs that cannot respond to mTOR signaling display significantly delayed HFSC activation and extended telogen.Unexpectedly,BMP signaling activity is dramatically prolonged in mTOR signaling-deficient HFs.Through both gain-and loss-of-function studies in vitro,we show that mTORC1 signaling negatively affects BMP signaling,which serves as a main mechanism whereby mTORC1 signaling facilitates HFSC activation.Indeed,in vivo suppression of BMP by its antagonist Noggin rescues the HFSC activation defect in mTORC1-null skin.Our findings reveal a critical role for mTOR signaling in regulating stem cell activation through counterbalancing BMP-mediated repression during hair regeneration.展开更多
Cashmere,also known as soft gold,is produced from the secondary hair follicles(SHFs)of cashmere goats.The number of SHFs determines the yield and quality of cashmere;therefore,it is of interest to investigate the tran...Cashmere,also known as soft gold,is produced from the secondary hair follicles(SHFs)of cashmere goats.The number of SHFs determines the yield and quality of cashmere;therefore,it is of interest to investigate the transcriptional profiles present during cashmere goat hair follicle development.However,mechanisms underlying this development process remain largely unexplored,and studies regarding hair follicle development mostly use a murine research model.In this study,to provide a comprehensive understanding of cellular heterogeneity and cell fate decisions,single-cell RNA sequencing was performed on 19,705 single cells of the dorsal skin from cashmere goat fetuses at induction(embryonic day 60;E60),organogenesis(E90),and cytodifferentiation(E120)stages.For the first time,unsupervised clustering analysis identified 16 cell clusters,and their corresponding cell types were also characterized.Based on lineage inference,a detailed molecular landscape was revealed along the dermal and epidermal cell lineage developmental pathways.Notably,our current data also confirmed the heterogeneity of dermal papillae from different hair follicle types,which was further validated by immunofluorescence analysis.The current study identifies different biomarkers during cashmere goat hair follicle development and has implications for cashmere goat breeding in the future.展开更多
The deep burn skin injures usually severely damage the dermis with the loss of hair follicle loss,which are difficult to regenerate.Furthermore,severe burns often accompanied with large amount of wound exudates making...The deep burn skin injures usually severely damage the dermis with the loss of hair follicle loss,which are difficult to regenerate.Furthermore,severe burns often accompanied with large amount of wound exudates making the wound moist,easily infected,and difficult to heal.Therefore,it is of great clinical significance to develop wound dressings to remove wound exudates and promote hair follicle regeneration.In this study,a sandwich-structured wound dressing(SWD)with Janus membrane property was fabricated by hot compression molding using hydrophilic zinc silicate bioceramics(Hardystonite,ZnCS)and hydrophobic polylactic acid(PLA).This unique organic/inorganic Janus membrane structure revealed excellent exudate absorption property and effectively created a dry wound environment.Meanwhile,the incorporation of ZnCS bioceramic particles endowed the dressing with the bioactivity to promote hair follicle regeneration and wound healing through the release of Zn^(2+)and SiO^(2-)_(3)ions,and this bioactivity of the wound dressing is mainly attributed to the synergistic effect of Zn^(2+)and SiO^(2-)_(3)to promote the recruitment,viability,and differentiation of hair follicle cells.Our study demonstrates that the utilization of the Janus membrane and synergistic effect of different type bioactive ions are effective approaches for the design of wound dressings for burn wound healing.展开更多
MG53 is an essential component of the cell membrane repair machinery,participating in the healing of dermal wounds.Here we develop a novel delivery system using recombinant human MG53(rhMG53)protein and a reactive oxy...MG53 is an essential component of the cell membrane repair machinery,participating in the healing of dermal wounds.Here we develop a novel delivery system using recombinant human MG53(rhMG53)protein and a reactive oxygen species(ROS)-scavenging gel to treat diabetic wounds.Mice with ablation of MG53 display defective hair follicle structure,and topical application of rhMG53 can promote hair growth in the mg53/mice.Cell lineage tracing studies reveal a physiological function of MG53 in modulating the proliferation of hair follicle stem cells(HFSCs).We find that rhMG53 protects HFSCs from oxidative stress-induced apoptosis and stimulates differentiation of HSFCs into keratinocytes.The cytoprotective function of MG53 is mediated by STATs and MAPK signaling in HFSCs.The thermosensitive ROS-scavenging gel encapsulated with rhMG53 allows for sustained release of rhMG53 and promotes healing of chronic cutaneous wounds and hair follicle development in the db/db mice.These findings support the potential therapeutic value of using rhMG53 in combination with ROS-scavenging gel to treat diabetic wounds.展开更多
MicroRNAs(miRNAs), small non-coding RNAs, are involved in many aspects of biological processes. Previous studies have indicated that mi RNAs are important for hair follicle development and growth. In our study, we fou...MicroRNAs(miRNAs), small non-coding RNAs, are involved in many aspects of biological processes. Previous studies have indicated that mi RNAs are important for hair follicle development and growth. In our study, we found by q RT-PCR that miR-148 b was signi ficantly upregulated in sheep wool follicle bulbs in anagen phase compared with the telogen phase of the hair follicle cycle. Overexpression of miR-148 b promoted proliferation of both HHDPC and HHGMC. By using the TOPFlash system we demonstrated that miR-148 b could activate Wnt/β-catenin pathway and b-catenin, cyc D, c-jun and PPARD were consistently upregulated accordingly.Furthermore, transcript factor nuclear factor of activated T cells type 5(NFAT5) and Wnt10 b were predicted to be the target of mi R-148 b and this was substantiated using a Dual-Luciferase reporter system. Subsequently NFAT5 was further identi fied as the target of mi R-148 b using western blotting. These results were considered to indicate that mi R-148 b could activate the Wnt/β-catenin signal pathway by targeting NFAT5 to promote the proliferation of human hair follicle cells.展开更多
This study was conducted to evaluate the effect of pyridoxine on the development of hair follicles in Rex rabbits and the underlying molecular mechanism.Two hundred 3-month-old Rex rabbits were randomly divided into 5...This study was conducted to evaluate the effect of pyridoxine on the development of hair follicles in Rex rabbits and the underlying molecular mechanism.Two hundred 3-month-old Rex rabbits were randomly divided into 5 groups and fed diets supplemented with 0,5,10,20,or 40 mg/kg pyridoxine.The hair follicle density on the dorsal skin and the gene and protein expression levels of components of the phosphoinositide 3-kinase(PI3 K)/protein kinase B(PKB or Akt),Wnt,Notch and bone morphogenetic protein(BMP)signalling pathways were measured.In addition,free hair follicles were isolated from Rex rabbits and cultured with pyridoxine in vitro to measure hair shaft growth.Furthermore,dermal papilla cells(DPC)were isolated from the skin of Rex rabbits and cultured with pyridoxine in vitro to measure the gene and protein expression levels of components of the PI3 K/Akt,Wnt,Notch and BMP signalling pathways.The results showed that the addition of dietary pyridoxine significantly increased the total follicle density,secondary follicle density,and secondary-to-primary ratio(S/P,P<0.05),that the growth ratio of hair stems was promoted by pyridoxine in basic culture medium,and that the growth length of tentacle hair follicles cultured in the pyridoxine group was longer than that in the control group(P<0.05).In addition,pyridoxine changed the DPC cycle progression and promoted cell proliferation,and appropriate concentrations of pyridoxine(10 and 20μmol/L)significantly inhibited cell apoptosis(P<0.05).Pyridoxine significantly affected the gene expression of components of the PI3 K/Akt,Wnt and Notch signalling pathways in the skin and DPC of Rex rabbits(P<0.05),increased the levels of phosphorylated catenin beta 1(CTNNB1)and Akt,and decreased the level of phosphorylated glycogen synthase kinase 3 beta(GSK-3β)(P<0.05).Therefore,the molecular mechanism by which pyridoxine promotes hair follicle density in Rex rabbits probably occurs through activation of the PI3 K/Akt,Wnt and Notch signalling pathways,prolonging hair follicle growth and delaying the onset of telogen.展开更多
Objective: To induce hair follicle regeneration in rat ear by microencapsulated dermal papillae (DP) cells.Methods: Intact dermal papillae were obtained from human scalp follicles which were digested with collagenase ...Objective: To induce hair follicle regeneration in rat ear by microencapsulated dermal papillae (DP) cells.Methods: Intact dermal papillae were obtained from human scalp follicles which were digested with collagenase I. The human hair DP cells were encapsulated with alginate-polylysine-alginate (APA) by a high-voltage electric field droplet generator. The diameters of the DP cell microcapsules were optimized by regulating the voltage, the distance be-tween the needle head and the solution surface and the injection speed. Then DP cell microencapsulations were xenotransplanted into ears of 20 SD rats with a novel method. One rat was killed every week at the postoperative 2-12 weeks and the implantation sites were biopsied for histo-logical observation.Results: The DP cell microencapsulations were found in a group of round, smooth and transparent microcapsules under a phase-contrast microscope. The optimal combina-tion of parameters to obtain 0.4 mm DP cell microcapsules was voltage 7.0 kV, injection speed 55 mm/h, and distance 10mm. After 4-12 weeks, 18 of 20 DP cell microcapsule implan-tations had produced high-density hair. Histological obser-vation indicated that both large follicles and sebaceous gland structures were formed in the rat ear within 3-12 weeks.Conclusions: These findings show that the DP cell microencapsulation maintain the capacity for initiating the follicle regeneration and can be considered as a substitute for fresh isolated dermal papillae.展开更多
Hair growth and regeneration represents a remarkable example of stem cell function.Recent progress emphasizes the micro-and macro-environment that controls the regeneration process.There is a shift from a stem cell-ce...Hair growth and regeneration represents a remarkable example of stem cell function.Recent progress emphasizes the micro-and macro-environment that controls the regeneration process.There is a shift from a stem cell-centered view toward the various layers of regulatory mechanisms that control hair regeneration,which include local growth factors,immune and neuroendocrine signals,and dietary and environmental factors.This is better suited for clinical applica-tion in multiple forms of hair disorders:in male pattern hair loss,the stem cells are largely preserved,but androgen signaling diminishes hair growth;in alopecia areata,an immune attack is targeted toward the growing hair follicle without abrogating its regeneration capability.Genome-wide association studies further revealed the genetic bases of these disorders,although the precise pathological mechanisms of the identified loci remain largely unknown.By analyzing the dysregulation of hair regeneration under pathological conditions,we can better address the complex interactions among stem cells,the differentiated progeny,and mesenchymal components,and highlight the critical role of macroenvironment adjustment that is essential for hair growth and regeneration.The poly-genetic origin of these disorders makes the study of hair regeneration an interesting and challenging field.展开更多
The molecular mechanisms of hair initiation and growth is one of the long-standing research programs in developmental biology.It has been suggested that for decades the existence of an inducing factor in the dermis th...The molecular mechanisms of hair initiation and growth is one of the long-standing research programs in developmental biology.It has been suggested that for decades the existence of an inducing factor in the dermis that is required for the initiation of hair development.Furthermore,various signaling families are involved in the reciprocal interactions between epidermis and dermis during hair follicle initiation and morphogenesis.Among them,the wingless-type MMTV integration site family(Wnt)is probably the earliest and most critical regulator.This review primarily focuses on the role of Wnt signaling in hair follicle induction and its relationship with the first dermal signal that initiates embryonic hair development.展开更多
基金supported by the China Agriculture Research System(CARS-39)。
文摘Background The quality and yield of cashmere fibre are closely related to the differentiation and development of secondary hair follicles in the skin of cashmere goats.The higher the density of secondary hair follicles,the higher the quality and yield of cashmere from the fleece.Development of secondary hair follicles commences in the embryonic stage of life and is completed 6 months after birth.Preliminary experimental results from our laboratory showed that melatonin(MT)treatment of goat kids after their birth could increase the density of secondary hair follicles and,thus,improve the subsequent yield and quality of cashmere.These changes in the secondary hair follicles resulted from increases in levels of antioxidant and expression of anti-apoptotic protein,and from a reduction in apoptosis.The present study was conducted to explore the molecular mechanism of MT-induced secondary hair follicle differentiation and development by using whole-genome analysis.Results MT had no adverse effect on the growth performance of cashmere kids but significantly improved the character of the secondary hair follicles and the quality of cashmere,and this dominant effect continued to the second year.Melatonin promotes the proliferation of secondary hair follicle cells at an early age.The formation of secondary hair follicles in the MT group was earlier than that in the control group in the second year.The genome-wide data results involved KEGG analysis of 1044 DEmRNAs,91 DElncRNAs,1054 DEcircRNAs,and 61 DEmiRNAs which revealed that the mitogen-activated protein kinase(MAPK)signaling pathway is involved in the development of secondary hair follicles,with key genes(FGF2,FGF21,FGFR3,MAPK3(ERK1))being up-regulated and expressed.We also found that the circMPP5 could sponged miR-211 and regulate the expression of MAPK3.Conclusions We conclude that MT achieves its effects by regulating the MAPK pathway through the circMPP5 sponged the miR-211,regulating the expression of MAPK3,to induce the differentiation and proliferation of secondary hair follicle cells.In addition there is up-regulation of expression of the anti-apoptotic protein causing reduced apoptosis of hair follicle cells.Collectively,these events increase the numbers of secondary hair follicles,thus improving the production of cashmere from these goats.
基金supported by grant from Guangdong Province University Student Innovation Training Program(No.201510560030)~~
文摘Objective To investigate the distribution and dynamic changes of both Wnt signaling molecules and CK15 throughoutthe three phases of the follicular cycle,and to explore the relationship between Wnt/β-catenin signaling and CK15 in rat whisker hair follicle(HF)growth cycles.Methods Hematoxylin-Eosin(HE)and immunofluorescence stains were used to characterize the expression patterns,including sites and levels of some representative proteins of both canonical and non-canonical Wnt signaling molecules,as well as HF epithelial stem cell marker CK15.Results The expression patterns of bothβ-catenin and Wnt5a were correlated with that of CK15.CK15 was only expressed in anagen.In catagen,β-catenin showed a massive depletion while Wnt5a noticeably increased.In telogen,high level expression ofβ-catenin and low level of Wnt5a were detected.Wnt10b and TCF3 were detected during the entire HF growth cycle.Conclusion These results suggest that Wnt5a is associated with the transition of anagen-catagen phase,accompanied by broad deletion ofβ-catenin and loss of CK15.WntlOb is important for the maintenance of HF activity and is related to the telogenanagen transition.
基金supported by the Open Project of Key Laboratory of SFGA on Conservation Biology of Rare Animals in the Giant Panda National Park(KLSFGAGP2020.009).
文摘With the completion of the draft assembly of the giant panda genome sequence,RNA sequencing technology has been widely used in genetic research on giant pandas.We used RNA-seq to examine black and white hair follicle samples from adult pandas.By comparison with the giant panda genome,75963 SNP loci were labeled,2426 differentially expressed genes(DEGs)were identified,and 2029 new genes were discovered,among which 631 were functionally annotated.A cluster analysis of the DEGs showed that they were mainly related to the Wnt signaling pathway,ECM–receptor interaction,the p53 signaling pathway,and ribosome processing.The enrichment results showed that there were significant differences in the regulatory networks of hair follicles with different colors during the transitional stage of hair follicle resting growth,which may play a regulatory role in melanin synthesis during growth.In conclusion,our results provide new insights and more data support for research on the color formation in giant pandas.
基金National Natural Science Foundation of China,No.82173446the Youth Training Program of the Army Medical University,No.2018XQN01.
文摘Hair follicle stem cells(HFSCs)in the bulge are a multipotent adult stem cell population.They can periodically give rise to new HFs and even regenerate the epidermis and sebaceous glands during wound healing.An increasing number of biomarkers have been used to isolate,label,and trace HFSCs in recent years.Considering more detailed data from single-cell transcriptomics technology,we mainly focus on the important HFSC molecular markers and their regulatory roles in this review.
基金supported partially by the National Nature Science Foundation of China(81830064,81721092,81701906)the National Key Research and Development Plan(2017YFC1103300)+3 种基金Funds of Chinese PLA General Hospital for Military Medical Inno-vation Research Project(CX19026)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)the Military Medical Research and Development Projects(AWS17J005,2019-126)Fostering Funds of Chinese PLA General Hospital for National Distinguished Young Scholar Science Fund(2017-JQPY-002).
文摘Background:Sweat glands(SGs)and hair follicles(HFs)are two important cutaneous appendages that play crucial roles in homeostatic maintenance and thermoregulation,and their interaction is involved in wound healing.SGs can be regenerated from mesenchymal stem cell-laden 3D bioprinted scaffolds,based on our previous studies,whereas regeneration of HFs could not be achieved in the same model.Due to the lack of an in vitro model,the underlying molecular mechanism of the interaction between SGs and HFs in regeneration could not be fully understood.The purpose of the present study was to establish an in vitro model of skin constructs with SGs and HFs and explore the interaction between these two appendages in regeneration.Methods:To investigate the interaction effects between SGs and HFs during their regeneration processes,a combined model was created by seeding HF spheroids on 3D printed SG scaffolds.The interaction between SG scaffolds and HF spheroids was detected using RNA expression and immunofluorescence staining.The effects of microenvironmental cues on SG and HF regeneration were analysed by altering seed cell types and plantar dermis homogenate in the scaffold.Results:According to this model,we overcame the difficulties in simultaneously inducing SG and HF regeneration and explored the interaction effects between SG scaffolds and HF spheroids.Surprisingly,HF spheroids promoted both SG and HF differentiation in SG scaffolds,while SG scaffolds promoted SG differentiation but had little effect on HF potency in HF spheroids.Specifically,microenvironmental factors(plantar dermis homogenate)in SG scaffolds effectively promoted SG and HF genesis in HF spheroids,no matter what the seed cell type in SG scaffolds was,and the promotion effects were persistent.Conclusions:Our approach elucidated a new model for SG and HF formation in vitro and provided an applicable platform to investigate the interaction between SGs and HFs in vitro.This platform might facilitate 3D skin constructs with multiple appendages and unveil the spatiotemporal molecular program of multiple appendage regeneration.
基金This work is supported by the Deanship of Scientific Research,Qassim University,KSA,project No.cavm-2018-1-14-S-3411The funding source did not involve in the design of the study and collection,analysis,and interpretation of data and in writing the manuscript。
文摘Clinical applications of cell therapy and tissue regeneration under different conditions need a multiplicity of adult stem cell sources.Up to date,little is available on the comparative isolation,characterization,proliferation,rapid amplification,and osteogenic/adipogenic differentiation of rat mesenchymal stem cells(MSCs)isolated from living bulge cells of the hair follicle(HF)and bone marrow(BM)from the same animal.This work hopes to use HF-MSCs as an additional adult stem cell source for research and application.After reaching 80%confluence,the cell counting,viability%,and yields of HF-MSCs and BM-MSCs were nearly similar.The viability%was 91.41±2.98 and 93.11±3.06 while the cells yield of initial seeding was 33.15±2.76 and 34.22±3.99 and of second passage was 28.76±1.01 and 29.56±3.11 for HF-MSCs and BM-MSCs respectively.Clusters of differentiation(CDs)analysis revealed that HF-MSCs were positively expressed CD34,CD73 and CD200 and negatively expressed CD45.BM-MSCs were positively expressed CD73 and CD200 and negatively expressed of CD34 and CD45.The proliferation of HFMSCs and BM-MSCs was determined by means of incorporation of Brd-U,population doubling time(PDT)assays and the quantity of formazan release.The percentage of Brd-U positive cells and PDT were relatively similar in both types of cells.The proliferation,as expressed by the quantity of formazan assay in confluent cells,revealed that the quantity of release by BM-MSCs was slightly higher than HF-MSCs.Adipogenic differentiated BM-MSCs showed moderate accumulation of oil red-O stained lipid droplets when compared to that of HF-MSCs which exhibited high stain.The total lipid concentration was significantly higher in adipogenic differentiated HF-MSCs than BMMSCs(P<0.05).It was found that activity of bone alkaline phosphatase and calcium concentration were significantly higher(P<0.01 and P<0.05 respectively)in osteogenic differentiated BM-MSCs than that of HF-MSCs.The present findings demonstrate that the HF-MSCs are very similar in most tested characteristics to BM-MSCs with the exception of differentiation.Additionally;no issues have been reported during the collection of HF-MSCs.Therefore,the HF may represent a suitable and accessible source for adult stem cells and can be considered an ideal cell source for adipogenesis research.
基金National Natural Science Foundation of China,No.81573067the Joint Construction Project between Jilin Province and Provincial Colleges,No.SXGJQY2017-12+2 种基金the Jilin Province Science and Technology Development Plan,No.20190304044YYthe Innovative Special Industry Fund Project in Jilin Province,No.2018C049-2the Open Research Project of the State Key Laboratory of Industrial Control Technology,Zhejiang University,China,No.ICT1800381.
文摘Hair follicles are easily accessible skin appendages that protect against cold and potential injuries.Hair follicles contain various pools of stem cells,such as epithelial,melanocyte,and mesenchymal stem cells(MSCs)that continuously self-renew,differentiate,regulate hair growth,and maintain skin homeostasis.Recently,MSCs derived from the dermal papilla or dermal sheath of the human hair follicle have received attention because of their accessibility and broad differentiation potential.In this review,we describe the applications of human hair follicle-derived MSCs(hHF-MSCs)in tissue engineering and regenerative medicine.We have described protocols for isolating hHF-MSCs from human hair follicles and their culture condition in detail.We also summarize strategies for maintaining hHF-MSCs in a highly proliferative but undifferentiated state after repeated in vitro passages,including supplementation of growth factors,3D suspension culture technology,and 3D aggregates of MSCs.In addition,we report the potential of hHF-MSCs in obtaining induced smooth muscle cells and tissue-engineered blood vessels,regenerated hair follicles,induced red blood cells,and induced pluripotent stem cells.In summary,the abundance,convenient accessibility,and broad differentiation potential make hHF-MSCs an ideal seed cell source of regenerative medical and cell therapy.
文摘Skin contains various populations of stem cells (SCs). Among these are hair follicle stem cells (HFSCs) in the bulge region. The behavior of HFSCs deserves to be widely studied due to the benefits to be derived from their identification, isolation, and amplification. Skin samples of newborn mice (n = 32) and human adults (n = 10) were used, and the bulge region was isolated and cultured. The isolation and characterization of cells were conducted through immunocytochemistry and immunofluorescence, using mainly CD34 and CD200 monoclonal antibodies. Initially, cells grew slowly from the explant around the bulge region, accruing cells with different morphology in both mouse and human, latter being mostly polygonal;the mouse cells reaching confluence faster (5 to 7 days) than the human (12 to 15 days). It was possible to isolate into subcultures cells with small size (10 - 13 μm diameter), round-shape, scant cytoplasm, central prominent nucleus and with nucleolus, which formed colonies, maintaining their phenotype in a high proportion (77% - 83% and 91% in mouse and human, respectively), without showing changes in their morphology during almost 7 months in the mouse cells, and a month and a half in the human. These results demonstrate that the selection, the isolation, and the conditioned mediums allowed population increases of bulge cells and indicate that cultured cells may retain their sternness in that they maintained their phenotypic characteristics, expressed specific markers for SCs, and showed a high proliferative capacity for long periods. Hair follicles, in mice and humans, are important repositories of multipotent stem cells, due to their tendency to differentiate into keratinocytes. Human HFSCs, obtained by depilation, preserve their potential for proliferation and prove to be easily accessible. This suggests that the bulge cells may present an alternative source of autologous stem cells for tissue engineering and regenerative medicine.
基金supported by the Taipei Tzu Chi Hospital through grants from the Buddhist Tzu Chi Medical Foundation under the Numbers TCRD-TPE-110-13 and TCRD-TPE-111-23,Taipei,Taiwan.
文摘Background:Cisplatin is a chemotherapeutic agent commonly used clinically for the treatment of various human cancers.Patients often reduce the use of cisplatin due to its side effects,which in turn affects its treatment.This study explored the mechanism of action of safflower extract as an adjuvant traditional Chinese medicine for chemotherapy.Methods:Primary human follicle dermal papilla cells(HFDPCs)were used as target cells for cisplatininduced damage to hair cells.Western blotting was used to investigate the molecular targets of cisplatin and safflower extract in causing HFDPCs damage.Cell survival and cell cycle were analyzed by mitochondrial staining reagent WST-1 and propidium iodide.Results:Cisplatin could reduce the viability of HFDPCs without causing cell death.Cisplatin increased the level of phospho-Rad17 in HFDPCs and activated the Chk1/Cdc25C signaling to reduce the expression of Cdc2 protein,thereby arresting the cells in the G2/M phase.The combination of safflower extract and the flavonoids could effectively inhibit the signal transduction of Rad17/Chk1/Cdc25 in cisplatin-treated cells and reduce the cell population in the G2/M phase.Finally,we also confirmed that safflower extract could effectively inhibit the damage to HFDPCs caused by cisplatin,mainly at the level of reducing the DNA damage caused by cisplatin.Conclusions:Safflower extract can be used as an adjuvant Chinese medicine for chemotherapy to reduce the damage caused by chemotherapy to normal hair follicle cells.
基金supported by the National Key Research and Development Program of China(No.2020YFA0804000)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16000000)+12 种基金the National Natural Science Foundation of China(Nos.82001477,81921006,82125011,92149301,92168201,91949209,92049304,92049116,32121001,32171447,82192863,82122024,82071588,32000500,81861168034,82271600 and 82201727)the National Key Research and Development Program of China(Nos.2018YFC2000100,2018YFA0107203,2020YFA0112200,2021YFF1201005,2021ZD0202401,2022YFA1103700 and 2021YFA1101401)CAS Project for Young Scientists in Basic Research(Nos.YSBR-076 and YSBR-012)the Program of the Beijing Natural Science Foundation(No.Z190019)K.C.Wong Education Foundation(Nos.GJTD-2019-06 and GJTD-2019-08)the Tencent Foundation(No.2021-1045)The Pilot Project for Public Welfare Development and Reform of Beijing-affiliated Medical Research Institutes(No.11000022T000000461062)Youth Innovation Promotion Association of CAS(Nos.E1CAZW0401 and 2022083)Young Elite Scientists Sponsorship Program by CAST(Nos.YESS20200012 and YESS20210002)the Informatization Plan of Chinese Academy of Sciences(Nos.CAS-WX2021SF-0301,CASWX2022SDC-XK14,and CAS-WX2021SF-0101)Beijing Hospitals Authority Youth Programme(No.QML20200802)the Open Research Program of State Key Laboratory of Membrane Biology(No.2021KF02)Grant from Key Laboratory of Stem Cells and Tissue Engineering(Sun Yat-Sen University),Ministry of Education(No.2021-A-001).
文摘Hair loss affects millions of people at some time in their life,and safe and efficient treatments for hair loss are a significant unmet medical need.We report that topical delivery of quercetin(Que)stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice.We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1αin endothelial cells.Skin administration of a HIF-1αagonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que.Together,these findings provide a molecular understanding for the efficacy of Que in hair regrowth,which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine,and suggest a route of pharmacological intervention that may promote hair regrowth.
基金supported by the National Natural Science Foundation of China(81772136,82172205,81902042)the Medical Scientific Research Foundation of Guangdong Province(A2018113)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2021A1515011453,2022A1515012160)the Special Fund of Foshan Summit plan(2019C002,2019D008,2019A006 and 2020A015)the Foundation of Foshan City(FS0AA-KJ218-1301-0034,2018AB003411).
文摘Hair follicle stem cells(HFSCs)reside in the bulge region of the outer root sheath of the hair follicle.They are considered slow-cycling cells that are endowed with multilineage differentiation potential and superior proliferative capacity.The normal morphology and periodic growth of HFSCs play a significant role in normal skin functions,wound repair and skin regeneration.The HFSCs involved in these pathophysiological processes are regulated by a series of cell signal transduction pathways,such as lymphoid enhancer factor/T-cell factor,Wnt/β-catenin,transforming growth factor-β/bone morphogenetic protein,Notch and Hedgehog.The mechanisms of the interactions among these signaling pathways and their regulatory effects on HFSCs have been previously studied,but many mechanisms are still unclear.This article reviews the regulation of hair follicles,HFSCs and related signaling pathways,with the aims of summarizing previous research results,revealing the regulatory mechanisms of HFSC proliferation and differentiation and providing important references and new ideas for treating clinical diseases.
基金This work was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA 01010202 to E.D.and XDA 04020202-20)the National Basic Research Program of China(2011CB710905 to E.D.)the National Natural Science Foundation of China(31201099 to S.L.and 31471287 to E.D.).
文摘Hair follicles(HFs)undergo cycles of degeneration(catagen),rest(telogen),and regeneration(anagen)phases.Anagen begins when the hair follicle stem cells(HFSCs)obtain sufficient activation cues to overcome suppressive signals,mainly the BMP pathway,from their niche cells.Here,we unveil that mTOR complex 1(mTORC1)signaling is activated in HFSCs,which coincides with the HFSC activation at the telogen-to-anagen transition.By using both an inducible conditional gene targeting strategy and a pharmacological inhibition method to ablate or inhibit mTOR signaling in adult skin epithelium before anagen initiation,we demonstrate that HFs that cannot respond to mTOR signaling display significantly delayed HFSC activation and extended telogen.Unexpectedly,BMP signaling activity is dramatically prolonged in mTOR signaling-deficient HFs.Through both gain-and loss-of-function studies in vitro,we show that mTORC1 signaling negatively affects BMP signaling,which serves as a main mechanism whereby mTORC1 signaling facilitates HFSC activation.Indeed,in vivo suppression of BMP by its antagonist Noggin rescues the HFSC activation defect in mTORC1-null skin.Our findings reveal a critical role for mTOR signaling in regulating stem cell activation through counterbalancing BMP-mediated repression during hair regeneration.
基金This study was supported by the National Natural Science Foundation of China(Grant Nos.31972556 and 31772573).
文摘Cashmere,also known as soft gold,is produced from the secondary hair follicles(SHFs)of cashmere goats.The number of SHFs determines the yield and quality of cashmere;therefore,it is of interest to investigate the transcriptional profiles present during cashmere goat hair follicle development.However,mechanisms underlying this development process remain largely unexplored,and studies regarding hair follicle development mostly use a murine research model.In this study,to provide a comprehensive understanding of cellular heterogeneity and cell fate decisions,single-cell RNA sequencing was performed on 19,705 single cells of the dorsal skin from cashmere goat fetuses at induction(embryonic day 60;E60),organogenesis(E90),and cytodifferentiation(E120)stages.For the first time,unsupervised clustering analysis identified 16 cell clusters,and their corresponding cell types were also characterized.Based on lineage inference,a detailed molecular landscape was revealed along the dermal and epidermal cell lineage developmental pathways.Notably,our current data also confirmed the heterogeneity of dermal papillae from different hair follicle types,which was further validated by immunofluorescence analysis.The current study identifies different biomarkers during cashmere goat hair follicle development and has implications for cashmere goat breeding in the future.
基金This work was supported by the National Key Research and Development Program of China(No.2016YFC1100201)the National Natural Science Foundation of China(No.81772078)+1 种基金the National Natural Science Foundation of China(No.81671830)the Science and Technology Commission of Shanghai Municipality(No.19441902300).
文摘The deep burn skin injures usually severely damage the dermis with the loss of hair follicle loss,which are difficult to regenerate.Furthermore,severe burns often accompanied with large amount of wound exudates making the wound moist,easily infected,and difficult to heal.Therefore,it is of great clinical significance to develop wound dressings to remove wound exudates and promote hair follicle regeneration.In this study,a sandwich-structured wound dressing(SWD)with Janus membrane property was fabricated by hot compression molding using hydrophilic zinc silicate bioceramics(Hardystonite,ZnCS)and hydrophobic polylactic acid(PLA).This unique organic/inorganic Janus membrane structure revealed excellent exudate absorption property and effectively created a dry wound environment.Meanwhile,the incorporation of ZnCS bioceramic particles endowed the dressing with the bioactivity to promote hair follicle regeneration and wound healing through the release of Zn^(2+)and SiO^(2-)_(3)ions,and this bioactivity of the wound dressing is mainly attributed to the synergistic effect of Zn^(2+)and SiO^(2-)_(3)to promote the recruitment,viability,and differentiation of hair follicle cells.Our study demonstrates that the utilization of the Janus membrane and synergistic effect of different type bioactive ions are effective approaches for the design of wound dressings for burn wound healing.
文摘MG53 is an essential component of the cell membrane repair machinery,participating in the healing of dermal wounds.Here we develop a novel delivery system using recombinant human MG53(rhMG53)protein and a reactive oxygen species(ROS)-scavenging gel to treat diabetic wounds.Mice with ablation of MG53 display defective hair follicle structure,and topical application of rhMG53 can promote hair growth in the mg53/mice.Cell lineage tracing studies reveal a physiological function of MG53 in modulating the proliferation of hair follicle stem cells(HFSCs).We find that rhMG53 protects HFSCs from oxidative stress-induced apoptosis and stimulates differentiation of HSFCs into keratinocytes.The cytoprotective function of MG53 is mediated by STATs and MAPK signaling in HFSCs.The thermosensitive ROS-scavenging gel encapsulated with rhMG53 allows for sustained release of rhMG53 and promotes healing of chronic cutaneous wounds and hair follicle development in the db/db mice.These findings support the potential therapeutic value of using rhMG53 in combination with ROS-scavenging gel to treat diabetic wounds.
基金supported by grants from the National High Technology Research and Development Program of China(2013AA102506)Regional Project of National Natural Science Foundation of China (31360534)
文摘MicroRNAs(miRNAs), small non-coding RNAs, are involved in many aspects of biological processes. Previous studies have indicated that mi RNAs are important for hair follicle development and growth. In our study, we found by q RT-PCR that miR-148 b was signi ficantly upregulated in sheep wool follicle bulbs in anagen phase compared with the telogen phase of the hair follicle cycle. Overexpression of miR-148 b promoted proliferation of both HHDPC and HHGMC. By using the TOPFlash system we demonstrated that miR-148 b could activate Wnt/β-catenin pathway and b-catenin, cyc D, c-jun and PPARD were consistently upregulated accordingly.Furthermore, transcript factor nuclear factor of activated T cells type 5(NFAT5) and Wnt10 b were predicted to be the target of mi R-148 b and this was substantiated using a Dual-Luciferase reporter system. Subsequently NFAT5 was further identi fied as the target of mi R-148 b using western blotting. These results were considered to indicate that mi R-148 b could activate the Wnt/β-catenin signal pathway by targeting NFAT5 to promote the proliferation of human hair follicle cells.
基金supported by the National Natural Science Foundation of China(31972594)Earmarked Fund for Modern Agro-industry Technology Research System(CARS-43-B-1)+2 种基金the Thoroughbred Project from Shandong Government(2017LZN008)Shandong Province Modern Agricultural Technology System Innovation Team(SDAIT-21)Funds of Shandong“Double Tops”Programme(SYL2017YSTD11)。
文摘This study was conducted to evaluate the effect of pyridoxine on the development of hair follicles in Rex rabbits and the underlying molecular mechanism.Two hundred 3-month-old Rex rabbits were randomly divided into 5 groups and fed diets supplemented with 0,5,10,20,or 40 mg/kg pyridoxine.The hair follicle density on the dorsal skin and the gene and protein expression levels of components of the phosphoinositide 3-kinase(PI3 K)/protein kinase B(PKB or Akt),Wnt,Notch and bone morphogenetic protein(BMP)signalling pathways were measured.In addition,free hair follicles were isolated from Rex rabbits and cultured with pyridoxine in vitro to measure hair shaft growth.Furthermore,dermal papilla cells(DPC)were isolated from the skin of Rex rabbits and cultured with pyridoxine in vitro to measure the gene and protein expression levels of components of the PI3 K/Akt,Wnt,Notch and BMP signalling pathways.The results showed that the addition of dietary pyridoxine significantly increased the total follicle density,secondary follicle density,and secondary-to-primary ratio(S/P,P<0.05),that the growth ratio of hair stems was promoted by pyridoxine in basic culture medium,and that the growth length of tentacle hair follicles cultured in the pyridoxine group was longer than that in the control group(P<0.05).In addition,pyridoxine changed the DPC cycle progression and promoted cell proliferation,and appropriate concentrations of pyridoxine(10 and 20μmol/L)significantly inhibited cell apoptosis(P<0.05).Pyridoxine significantly affected the gene expression of components of the PI3 K/Akt,Wnt and Notch signalling pathways in the skin and DPC of Rex rabbits(P<0.05),increased the levels of phosphorylated catenin beta 1(CTNNB1)and Akt,and decreased the level of phosphorylated glycogen synthase kinase 3 beta(GSK-3β)(P<0.05).Therefore,the molecular mechanism by which pyridoxine promotes hair follicle density in Rex rabbits probably occurs through activation of the PI3 K/Akt,Wnt and Notch signalling pathways,prolonging hair follicle growth and delaying the onset of telogen.
文摘Objective: To induce hair follicle regeneration in rat ear by microencapsulated dermal papillae (DP) cells.Methods: Intact dermal papillae were obtained from human scalp follicles which were digested with collagenase I. The human hair DP cells were encapsulated with alginate-polylysine-alginate (APA) by a high-voltage electric field droplet generator. The diameters of the DP cell microcapsules were optimized by regulating the voltage, the distance be-tween the needle head and the solution surface and the injection speed. Then DP cell microencapsulations were xenotransplanted into ears of 20 SD rats with a novel method. One rat was killed every week at the postoperative 2-12 weeks and the implantation sites were biopsied for histo-logical observation.Results: The DP cell microencapsulations were found in a group of round, smooth and transparent microcapsules under a phase-contrast microscope. The optimal combina-tion of parameters to obtain 0.4 mm DP cell microcapsules was voltage 7.0 kV, injection speed 55 mm/h, and distance 10mm. After 4-12 weeks, 18 of 20 DP cell microcapsule implan-tations had produced high-density hair. Histological obser-vation indicated that both large follicles and sebaceous gland structures were formed in the rat ear within 3-12 weeks.Conclusions: These findings show that the DP cell microencapsulation maintain the capacity for initiating the follicle regeneration and can be considered as a substitute for fresh isolated dermal papillae.
基金ZY is supported by the National Natural Science Foundation of China(NSFC 31871468)the Shenzhen University Stable Support Program(20200808172413001).
文摘Hair growth and regeneration represents a remarkable example of stem cell function.Recent progress emphasizes the micro-and macro-environment that controls the regeneration process.There is a shift from a stem cell-centered view toward the various layers of regulatory mechanisms that control hair regeneration,which include local growth factors,immune and neuroendocrine signals,and dietary and environmental factors.This is better suited for clinical applica-tion in multiple forms of hair disorders:in male pattern hair loss,the stem cells are largely preserved,but androgen signaling diminishes hair growth;in alopecia areata,an immune attack is targeted toward the growing hair follicle without abrogating its regeneration capability.Genome-wide association studies further revealed the genetic bases of these disorders,although the precise pathological mechanisms of the identified loci remain largely unknown.By analyzing the dysregulation of hair regeneration under pathological conditions,we can better address the complex interactions among stem cells,the differentiated progeny,and mesenchymal components,and highlight the critical role of macroenvironment adjustment that is essential for hair growth and regeneration.The poly-genetic origin of these disorders makes the study of hair regeneration an interesting and challenging field.
基金This work was supported by the Shandong Provincial Natural Science Foundation,China(grant number ZR2014HM017)the Fundamental Research Fund of Shandong University.
文摘The molecular mechanisms of hair initiation and growth is one of the long-standing research programs in developmental biology.It has been suggested that for decades the existence of an inducing factor in the dermis that is required for the initiation of hair development.Furthermore,various signaling families are involved in the reciprocal interactions between epidermis and dermis during hair follicle initiation and morphogenesis.Among them,the wingless-type MMTV integration site family(Wnt)is probably the earliest and most critical regulator.This review primarily focuses on the role of Wnt signaling in hair follicle induction and its relationship with the first dermal signal that initiates embryonic hair development.
