The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have bee...The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have been made in the treatment of neovascular AMD,effective intervention for atrophic AMD is largely absent.The adequate knowledge of RPE pathology is hindered by a lack of the patients'RPE datasets,especially at the single-cell resolution.In the current study,we delved into a large-scale single-cell resource of AMD donors,in which RPE cells were occupied in a substantial proportion.Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD.Both in vivo and in vitro models revealed that carboxypeptidase X,M14 family member 2(CPXM2),was specifically expressed in the RPE cells of atrophic AMD,which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells.Additionally,silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model.Thus,our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD.展开更多
Background:Systemic lupus erythematosus(SLE)is a complex chronic autoimmune disease with no known cure.However,the regulatory mechanism of immunity-related genes is not fully understood in SLE.In order to explore new ...Background:Systemic lupus erythematosus(SLE)is a complex chronic autoimmune disease with no known cure.However,the regulatory mechanism of immunity-related genes is not fully understood in SLE.In order to explore new therapeutic targets,we used bioinformatical methods to analyze a series of data.Methods:After downloading and processing the data from Gene Expression Omnibus database,the differentially expressed genes of SLE were analyzed.CIBERSORT algorithm was used to analyze the immune infiltration of SLE.Based on single-cell RNA-sequencing data,the role of immune-related genes in SLE and its target organ(kidney)were analyzed.Key transcription factors affecting immune-related genes were identified.Cell-cell communication networks in SLE were analyzed.Results:In total,15 hub genes and 4 transcription factors were found in the bulk data.Monocytes and macrophages in GSE81622(SLE)showed more infiltration.There were four cell types were annotated in scRNA sequencing dataset(GSE135779),as follows T cells,monocyte,NK cells and B cells.Immunity-related genes were overexpressed in monocytes.Conclusion:The present study shows that immune-related genes affect SLE through monocytes and play an important role in target organ renal injury.展开更多
Barley(Hordeum vulgare L.)is one of the earliest domesticated crop species and ranked as the fourth largest cereal production worldwide.Forward genetic studies in barley have greatly advanced plant genetics during the...Barley(Hordeum vulgare L.)is one of the earliest domesticated crop species and ranked as the fourth largest cereal production worldwide.Forward genetic studies in barley have greatly advanced plant genetics during the last century;however,most genes are identified by the conventional mapping method.Array genotyping and exome-capture sequencing have also been successfully used to target the causal mutation in barley populations,but these techniques are not widely adopted because of associated costs and partly due to the huge genome size of barley.This review summarizes three mapping cases of barley cuticle mutants in our laboratory with the help of RNA-sequencing.The causal mutations have been successfully identified for two of them and the target genes are located in the pericentromeric regions.Detailed information on the mapping-by-sequencing,mapping-and-sequencing,and RNA-sequencing assisted linkage mapping are presented and some limitations and challenges on the mapping assisted by RNA sequencing are also discussed.The alternative and elegant methods presented in this review may greatly accelerate forward genetics of barley mapping,especially for laboratories without large funding.展开更多
Human cytomegalovirus(HCMV)is a common herpesvirus that persistently infects a large portion of the world's population.Despite the robust host immune response,HCMV is able to replicate,evade host defenses,and esta...Human cytomegalovirus(HCMV)is a common herpesvirus that persistently infects a large portion of the world's population.Despite the robust host immune response,HCMV is able to replicate,evade host defenses,and establish latency throughout the lifespan by developing multiple immunomodulatory strategies,making the studies on the interaction between HCMV infection and host response particularly important.HCMV has a strict host specificity that specifically infects humans.Therefore,most of the in vivo researches of HCMV rely on clinical samples.Fortunately,the establishment of humanized mouse models allows for convenient in-lab animal experiments involving HCMV infection.Single-cell RNA sequencing enables the study of the relationship between viral and host gene expressions at the single-cell level within host cells.In this study,we assessed the gene expression alterations of PBMCs at the single-cell level within HCMV-infected humanized mice,which sheds light onto the virus-host interactions in the context of HCMV infection of humanized mice and provides a valuable dataset for the related researches.展开更多
Aberrant biological information occurs naturally at exposure to bisphenol A or its alternatives,which was associated with the occurrence and development of breast cancer.However,the potential molecular variation in ge...Aberrant biological information occurs naturally at exposure to bisphenol A or its alternatives,which was associated with the occurrence and development of breast cancer.However,the potential molecular variation in gene expression during the breast tumor development is still unclear.Herein,high throughput RNA sequencing(RNA-Seq)and bioinformatics analysis were used to investigate the variation of tumor-mRNA profile exposed with BPS5(5µg/kg bw/day)or BPS50(50µg/kg bw/day)in tumor development-associated MMTV-PyMT transgenic mouse model.Meanwhile,we analyzed the dose-effects of bisphenol S(BPS)and BPS-induced tumor development on the gene level exhaustively.In dose-effect aspects of BPS,the increased concentration of BPS significantly changed the numbers and enrichment pathway of differentially expressed genes(DEGs),especially the enrichment pathways involved in up-regulated genes including ribosome,peroxisome proliferators-activated receptor(PPAR)signaling pathway and progesterone-mediated oocyte maturation pathway.In effects of BPS exposure to tumor development,expression of IgκC,Zfp385b,Cldn10,Pgr and Snord14d has changed significantly throughout the tumor development.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)results obtained from BPS-induced tumor development showed that the functional classifications were intensively altered with an extension of time in high-dose BPS groups.The acquired DEGs and pathway information could help with the accurate exploration of molecular mechanisms of tumor development,screening of molecular targets of breast cancer,and toxicological evaluation of environmental pollutants.展开更多
As a disorder of lipid metabolism,hyperlipidemia(HLP)is characterized by elevated levels of lipids in the blood circulation.It is consistently related to the development of cardiovascular events and diseases associate...As a disorder of lipid metabolism,hyperlipidemia(HLP)is characterized by elevated levels of lipids in the blood circulation.It is consistently related to the development of cardiovascular events and diseases associated with metabolic syndrome.Alismatis Rhizoma decoction(ARD),a well-known traditional Chinese medicine prescription,has long been used for treating vertigo,which is a symptom experienced by HLP patients.In this study,we aimed to investigate the hyperlipidemic activity and the potential molecular mechanisms of ARD in HLP rats at the transcriptional level.RNA sequencing and transcriptome analysis were performed collaboratively,including analysis of differentially expressed genes(DEGs),GO functions,and KEGG pathway analysis.The results showed that 1981 DEGs(1370 upregulated and 611 downregulated)were identified in the HFD group compared with the CON group.Moreover,474 DEGs(350 upregulated and 124 downregulated)were detected in the ARD group compared with the HFD group.Furthermore,GO analysis revealed that DEGs were mainly involved in the following functions:developmental process,response to an external stimulus,ion transport,alcohol binding,and plasma membrane part.Pathway analysis suggested that these DEGs were significantly enriched in bile secretion,malaria,cell adhesion molecules,retinol metabolism,the sphingolipid signaling pathway,chemical carcinogenesis,and the T cell receptor signaling pathway.In conclusion,our study demonstrated that ARD alleviated the lipid metabolism disorder caused by HLP through multiple mechanisms,which provided vital scientific evidence for further pharmacological studies of ARD.展开更多
Recently,the emergence of single-cell RNA-sequencing(scRNA-seq)technology makes it possible to solve biological problems at the single-cell resolution.One of the critical steps in cellular heterogeneity analysis is th...Recently,the emergence of single-cell RNA-sequencing(scRNA-seq)technology makes it possible to solve biological problems at the single-cell resolution.One of the critical steps in cellular heterogeneity analysis is the cell type identification.Diverse scRNA-seq clustering methods have been proposed to partition cells into clusters.Among all the methods,hierarchical clustering and spectral clustering are the most popular approaches in the downstream clustering analysis with different preprocessing strategies such as similarity learning,dropout imputation,and dimensionality reduction.In this study,we carry out a comprehensive analysis by combining different strategies with these two categories of clustering methods on scRNA-seq datasets under different biological conditions.The analysis results show that the methods with spectral clustering tend to perform better on datasets with continuous shapes in two-dimension,while those with hierarchical clustering achieve better results on datasets with obvious boundaries between clusters in two-dimension.Motivated by this finding,a new strategy,called QRS,is developed to quantitatively evaluate the latent representative shape of a dataset to distinguish whether it has clear boundaries or not.Finally,a data-driven clustering recommendation method,called DDCR,is proposed to recommend hierarchical clustering or spectral clustering for scRNA-seq data.We perform DDCR on two typical single cell clustering methods,SC3 and RAFSIL,and the results show that DDCR recommends a more suitable downstream clustering method for different scRNA-seq datasets and obtains more robust and accurate results.展开更多
Background:The growing male reproductive diseases have been linked to higher exposure to certain environmental compounds such as 2,2,4,4-tetrabromodiphenyl ether(BDE47)that are widely distributed in the food chain.How...Background:The growing male reproductive diseases have been linked to higher exposure to certain environmental compounds such as 2,2,4,4-tetrabromodiphenyl ether(BDE47)that are widely distributed in the food chain.However,the specific underlying molecular mechanisms for BDE47-induced male reproductive toxicity are not completely understood.Methods:Here,for the first time,advanced single-cell RNA sequencing(ScRNA-seq)was employed to dissect BDE47-induced prepubertal testicular toxicity in mice from a pool of 76859 cells.Results:Our ScRNA-seq results revealed shared and heterogeneous information of differentially expressed genes,signaling pathways,transcription factors,and ligands-receptors in major testicular cell types in mice upon BDE47 treatment.Apart from disruption of hormone homeostasis,BDE47 was discovered to downregulate multiple previously unappreciated pathways such as double-strand break repair and cytokinesis pathways,indicative of their potential roles involved in BDE47-induced testicular injury.Interestingly,transcription factors analysis of ScRNA-seq results revealed that Kdm5b(lysine-specific demethylase 5B),a key transcription factor required for spermatogenesis,was downregulated in all germ cells as well as in Sertoli and telocyte cells in BDE47-treated testes of mice,suggesting its contribution to BDE47-induced impairment of spermatogenesis.Conclusions:Overall,for the first time,we established the molecular cell atlas of mice testes to define BDE47-induced prepubertal testicular toxicity using the ScRNA-seq approach,providing novel insight into our understanding of the underlying mechanisms and pathways involved in BDE47-associated testicular injury at a single-cell resolution.Our results can serve as an important resource to further dissect the potential roles of BDE47,and other relevant endocrine-disrupting chemicals,in inducing male reproductive toxicity.展开更多
With the support by the National Natural Science Foundation of China,the research team directed by Prof.Tang FuChou(汤富酬)at the Biomedical Pioneering Innovation Center(BIOPIC),College of life Sciences,Peking Univers...With the support by the National Natural Science Foundation of China,the research team directed by Prof.Tang FuChou(汤富酬)at the Biomedical Pioneering Innovation Center(BIOPIC),College of life Sciences,Peking University,and Prof.Qiao Jie(乔杰)at Peking University Third Hospital recently dissected the gene expression profiles of the four main organs of human fetal digestive tract and the adult large intestine in vivo at single-cell resolution,which was published in Nature Cell Biology(2018,20(6):721-734).The first author of the paper is associate professor Gao Shuai(高帅)at the College of Animal Science and Technology,China Agricultural University.展开更多
Verticillium dahliae causes significant losses in cotton production.To reveal the mechanism of the defense response to V.dahliae in cotton,transcriptomic analyses were performed using cotton cultivars M138(V.dahliae-r...Verticillium dahliae causes significant losses in cotton production.To reveal the mechanism of the defense response to V.dahliae in cotton,transcriptomic analyses were performed using cotton cultivars M138(V.dahliae-resistant)and P2(V.dahliae-susceptible).The results revealed 11,076 and 6,640 differentially expressed genes(DEGs)in response to V.dahliae,respectively.The weighted gene co-expression network analysis of 4,633 transcription factors(TFs)indicated a“MEblue”module containing 654 TFs that strongly correlate with resistance to V.dahliae.Among these TFs,the ethylene response factor Ghi_A05G10166(GhERF91)was identified as a putative hub gene with a defense response against V.dahliae.A virus-induced gene silencing assay and exogenous application of ethephon showed that GhERF91 is activated by ethylene and positively regulates the response to V.dahliae exposure in cotton.This study provides fundamental transcriptome data and a putative causal gene(GhERF91)associated with resistance to V.dahliae,as well as genetic resources for breeding V.dahliae-resistant cotton.展开更多
Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment o...Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.展开更多
Background As Holstein calves are susceptible to gastrointestinal disorders during the first week of life,understanding how intestinal immune function develops in neonatal calves is important to promote better intesti...Background As Holstein calves are susceptible to gastrointestinal disorders during the first week of life,understanding how intestinal immune function develops in neonatal calves is important to promote better intestinal health.Feeding probiotics in early life may contribute to host intestinal health by facilitating beneficial bacteria colonization and developing intestinal immune function.The objective of this study was to characterize the impact of early life yeast supplementation and growth on colon mucosa-attached bacteria and host immune function.Results Twenty Holstein bull calves received no supplementation(CON)or Saccharomyces cerevisiae boulardii(SCB)from birth to 5 d of life.Colon tissue biopsies were taken within 2 h of life(D0)before the first colostrum feeding and 3 h after the morning feeding at d 5 of age(D5)to analyze mucosa-attached bacteria and colon transcriptome.Metagenome sequencing showed that there was no difference inαandβdiversity of mucosa-attached bacteria between day and treatment,but bacteria related to diarrhea were more abundant in the colon mucosa on D0 compared to D5.In addition,q PCR indicated that the absolute abundance of Escherichia coli(E.coli)decreased in the colon mucosa on D5 compared to D0;however,that of Bifidobacterium,Lactobacillus,and Faecalibacterium prausnitzii,which could competitively exclude E.coli,increased in the colon mucosa on D5 compared to D0.RNA-sequencing showed that there were no differentially expressed genes between CON and SCB,but suggested that pathways related to viral infection such as“Interferon Signaling”were activated in the colon mucosa of D5 compared to D0.Conclusions Growth affected mucosa-attached bacteria and host immune function in the colon mucosa during the first 5 d of life in dairy calves independently of SCB supplementation.During early life,opportunistic pathogens may decrease due to intestinal environmental changes by beneficial bacteria and/or host immune function.Predicted activation of immune function-related pathways may be the result of host immune function development or suggest other antigens in the intestine during early life.Further studies focusing on the other antigens and host immune function in the colon mucosa are required to better understand intestinal immune function development.展开更多
The Chinese crested duck is a unique duck breed having a bulbous feather shape on its duck head.However,the mechanisms involved in its formation and development are unclear.In the present study,RNA sequencing analysis...The Chinese crested duck is a unique duck breed having a bulbous feather shape on its duck head.However,the mechanisms involved in its formation and development are unclear.In the present study,RNA sequencing analysis was performed on the crested tissues of 6 Chinese crested ducks and the scalp tissues of 6 cherry valley ducks(CVs)from 2 developmental stages.This study identified 261 differentially expressed genes(DEGs),122 upregulated and 139 downregulated,in the E28 stage and 361 DEGs,154 upregulated and 207 downregulated in the D42 stage between CC and CV ducks.The subsequent results of weighted gene co-expression network analysis(WGCNA)revealed that the turquoise and cyan modules were associated with the crest trait in the D42 stage,meanwhile,the green,brown,and pink modules were associated with the crest trait in the E28 stage.Venn analysis of the DEGs and WGCNA showed that 145 and 45 genes are associated between the D42 and E28 stages,respectively.The expression of WNT16,BMP2,SLC35F2,SLC6A15,APOBEC2,ABHD6,TNNC2,MYL1,and TNNI2 were verified by real-time quantitative PCR.This study provides an approach to reveal the molecular mechanisms underlying the crested trait development.展开更多
BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated ...BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.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
Mucin genes are the main component of mucus. The sea anemone species, Aulactinia veratra (Phylum Cnidaria) contains different types of mucin genes. In the intertidal zone, A. veratra is found to be exposed to air duri...Mucin genes are the main component of mucus. The sea anemone species, Aulactinia veratra (Phylum Cnidaria) contains different types of mucin genes. In the intertidal zone, A. veratra is found to be exposed to air during the low tide and produces large quantities of mucus as an external covering. The relation between low tide and mucus secretion is still unclear, and what is the role of mucin during arial exposure is not yet investigated. This study hypothesised that the mucin genes in A. veratra would have significantly high expression in response to aerial exposure. Therefore, the aim of current study was to examine and analyses the response of A. veratra mucins in response to an experiment involving three hours of aerial exposure. To achieve this, aim the RNA-sequencing and bioinformatics analyses were used to examine the expression profile of A. veratra mucin genes in response to aerial exposure. The generated results have shown that, Mucin4-like and mucin5B-like were up-regulated in response to the three hours of aerial exposure in A. veratra. This finding shows a significant role of mucin5B-like and mucin4-like genes in response to air stress at low tide. The data generated from this study could be used in conjunction with future mucin gene studies of sea anemones and other cnidarians to compare A. veratra mucin gene expression results across time, and to extend our understanding of mucin stress response in this phylum.展开更多
Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especiall...Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis stages.To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver fibrosis.Integrative analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial cells.Moreover,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these processes.These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver fibrosis.Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.展开更多
Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion(II/R)injury by single-cell RNA sequencing.For enterocyte cells,11 subclusters were found,in which enterocyte clus...Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion(II/R)injury by single-cell RNA sequencing.For enterocyte cells,11 subclusters were found,in which enterocyte cluster 1(EC1),enterocyte cluster 3(EC3),and enterocyte cluster 8(EC8)were newly discovered cells in ischemia 45 min/reperfusion 720 min(I 45 min/R 720 min)group.EC1 and EC3 played roles in digestion and absorption,and EC8 played a role in cell junctions.For TA cells,after ischemia 45 min/reperfusion 90 min(I 45 min/R 90 min),many TA cells at the stage of proliferation were identified.For Paneth cells,Paneth cluster 3 was observed in the resting state of normal jejunum.After I 45 min/R 90 min,three new subsets were found,in which Paneth cluster 1 had good antigen presentation activity.The main functions of goblet cells were to synthesize and secrete mucus,and a novel subcluster(goblet cluster 5)with highly proliferative ability was discovered in I 45 min/R 90 min group.As a major part of immune system,the changes in T cells with important roles were clarified.Notably,enterocyte cells secreted Guca2b to interact with Gucy2c receptor on the membranes of stem cells,TA cells,Paneth cells,and goblet cells to elicit intercellular communication.One marker known as glutathione S-transferase mu 3(GSTM3)affected intestinal mucosal barrier function by adjusting mitogen-activated protein kinases(MAPK)signaling during II/R injury.The data on the heterogeneity of intestinal cells,cellular communication and the mechanism of GSTM3 provide a cellular basis for treating II/R injury.展开更多
Over the past decade,the advent of single cell RNA-sequencing has revolutionized the approach in cellular transcriptomics research.The current technology offers an unbiased platform to understand how genotype correlat...Over the past decade,the advent of single cell RNA-sequencing has revolutionized the approach in cellular transcriptomics research.The current technology offers an unbiased platform to understand how genotype correlates to phenotype.Single-cell omics applications in gastrointestinal(GI)research namely inflammatory bowel disease(IBD)has become popular in the last few years with multiple publications as single-cell omics techniques can be applied directly to the target organ,the GI tract at the tissue level.Through examination of mucosal tissue and peripheral blood in IBD,the recent boom in single cell research has identified a myriad of key immune players from enterocytes to tissue resident memory T cells,and explored functional heterogeneity within cellular subsets previously unreported.As we begin to unravel the complex mucosal immune system in states of health and disease like IBD,the power of exploration through single-cell omics can change our approach to translational research.As novel techniques evolve through multiplexing single-cell omics and spatial transcriptomics come to the forefront,we can begin to fully comprehend the disease IBD and better design targets of treatment.In addition,hopefully these techniques can ultimately begin to identify biomarkers of therapeutic response and answer clinically relevant questions in how to tailor individual therapy to patients through personalized medicine.展开更多
基金the National Natural Science Foundation of China(Grant Nos.81970821 and 82271100 to Q.L.).
文摘The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have been made in the treatment of neovascular AMD,effective intervention for atrophic AMD is largely absent.The adequate knowledge of RPE pathology is hindered by a lack of the patients'RPE datasets,especially at the single-cell resolution.In the current study,we delved into a large-scale single-cell resource of AMD donors,in which RPE cells were occupied in a substantial proportion.Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD.Both in vivo and in vitro models revealed that carboxypeptidase X,M14 family member 2(CPXM2),was specifically expressed in the RPE cells of atrophic AMD,which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells.Additionally,silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model.Thus,our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD.
文摘Background:Systemic lupus erythematosus(SLE)is a complex chronic autoimmune disease with no known cure.However,the regulatory mechanism of immunity-related genes is not fully understood in SLE.In order to explore new therapeutic targets,we used bioinformatical methods to analyze a series of data.Methods:After downloading and processing the data from Gene Expression Omnibus database,the differentially expressed genes of SLE were analyzed.CIBERSORT algorithm was used to analyze the immune infiltration of SLE.Based on single-cell RNA-sequencing data,the role of immune-related genes in SLE and its target organ(kidney)were analyzed.Key transcription factors affecting immune-related genes were identified.Cell-cell communication networks in SLE were analyzed.Results:In total,15 hub genes and 4 transcription factors were found in the bulk data.Monocytes and macrophages in GSE81622(SLE)showed more infiltration.There were four cell types were annotated in scRNA sequencing dataset(GSE135779),as follows T cells,monocyte,NK cells and B cells.Immunity-related genes were overexpressed in monocytes.Conclusion:The present study shows that immune-related genes affect SLE through monocytes and play an important role in target organ renal injury.
基金grants from the National Natural Science Foundation of China(No.41621001,No.31870381,and No.31970352)by the Youth Innovation Promotion Association,CAS(2018463).
文摘Barley(Hordeum vulgare L.)is one of the earliest domesticated crop species and ranked as the fourth largest cereal production worldwide.Forward genetic studies in barley have greatly advanced plant genetics during the last century;however,most genes are identified by the conventional mapping method.Array genotyping and exome-capture sequencing have also been successfully used to target the causal mutation in barley populations,but these techniques are not widely adopted because of associated costs and partly due to the huge genome size of barley.This review summarizes three mapping cases of barley cuticle mutants in our laboratory with the help of RNA-sequencing.The causal mutations have been successfully identified for two of them and the target genes are located in the pericentromeric regions.Detailed information on the mapping-by-sequencing,mapping-and-sequencing,and RNA-sequencing assisted linkage mapping are presented and some limitations and challenges on the mapping assisted by RNA sequencing are also discussed.The alternative and elegant methods presented in this review may greatly accelerate forward genetics of barley mapping,especially for laboratories without large funding.
基金supported by the National Key R&D Program of China(2023YFC23066000 to Y.R.)the National Natural Science Foundation of China(32100106 to Y.R.,and U21A20423 and 32225004 to X.Z.)+2 种基金the CAS Youth Innovation Promotion Association(2023351 to Y.R.)Hubei Province Natural Science Funds(2023AFB582 to Y.R.and 2023AFA008 to X.Z)the Fund of the Science and Technology Bureau of Wuhan(2023020201010086 to Y.R.).
文摘Human cytomegalovirus(HCMV)is a common herpesvirus that persistently infects a large portion of the world's population.Despite the robust host immune response,HCMV is able to replicate,evade host defenses,and establish latency throughout the lifespan by developing multiple immunomodulatory strategies,making the studies on the interaction between HCMV infection and host response particularly important.HCMV has a strict host specificity that specifically infects humans.Therefore,most of the in vivo researches of HCMV rely on clinical samples.Fortunately,the establishment of humanized mouse models allows for convenient in-lab animal experiments involving HCMV infection.Single-cell RNA sequencing enables the study of the relationship between viral and host gene expressions at the single-cell level within host cells.In this study,we assessed the gene expression alterations of PBMCs at the single-cell level within HCMV-infected humanized mice,which sheds light onto the virus-host interactions in the context of HCMV infection of humanized mice and provides a valuable dataset for the related researches.
基金supported by the National Natural Science Foundation of China(No.22176195)the Natural Science Foundation of Guangdong Province,China(No.2021A1515010171)+4 种基金the Key Program of Fundamental Research in Shenzhen,China(NoJCYJ20210324115811031)the Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression,China(No.ZDSYS20220606100606014)the Shenzhen Key Medical Discipline Construction Fund,China(No.SZXK052)the Clinical Research Project of Shenzhen Second People’s Hospital,China(No.20203357001)the Guangdong Basic and Applied Basic Research Foundation,China(No.2021A1515110096).
文摘Aberrant biological information occurs naturally at exposure to bisphenol A or its alternatives,which was associated with the occurrence and development of breast cancer.However,the potential molecular variation in gene expression during the breast tumor development is still unclear.Herein,high throughput RNA sequencing(RNA-Seq)and bioinformatics analysis were used to investigate the variation of tumor-mRNA profile exposed with BPS5(5µg/kg bw/day)or BPS50(50µg/kg bw/day)in tumor development-associated MMTV-PyMT transgenic mouse model.Meanwhile,we analyzed the dose-effects of bisphenol S(BPS)and BPS-induced tumor development on the gene level exhaustively.In dose-effect aspects of BPS,the increased concentration of BPS significantly changed the numbers and enrichment pathway of differentially expressed genes(DEGs),especially the enrichment pathways involved in up-regulated genes including ribosome,peroxisome proliferators-activated receptor(PPAR)signaling pathway and progesterone-mediated oocyte maturation pathway.In effects of BPS exposure to tumor development,expression of IgκC,Zfp385b,Cldn10,Pgr and Snord14d has changed significantly throughout the tumor development.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)results obtained from BPS-induced tumor development showed that the functional classifications were intensively altered with an extension of time in high-dose BPS groups.The acquired DEGs and pathway information could help with the accurate exploration of molecular mechanisms of tumor development,screening of molecular targets of breast cancer,and toxicological evaluation of environmental pollutants.
基金The Basic Research Project of Fujian Provincial Public Welfare Research Institute(Grant No.2018R1031-3)Medical Innovation Project of Fujian Provincial Health Commission(Grant No.2018-CX-15)+1 种基金Basic Research Project of Fujian Provincial Public Welfare Research Institute,China(Grant No.2019R1011-5)High-Level Hospital grants(Grant No.2017GL-001)from Fujian Provincial Hospita,Fujian Province,China。
文摘As a disorder of lipid metabolism,hyperlipidemia(HLP)is characterized by elevated levels of lipids in the blood circulation.It is consistently related to the development of cardiovascular events and diseases associated with metabolic syndrome.Alismatis Rhizoma decoction(ARD),a well-known traditional Chinese medicine prescription,has long been used for treating vertigo,which is a symptom experienced by HLP patients.In this study,we aimed to investigate the hyperlipidemic activity and the potential molecular mechanisms of ARD in HLP rats at the transcriptional level.RNA sequencing and transcriptome analysis were performed collaboratively,including analysis of differentially expressed genes(DEGs),GO functions,and KEGG pathway analysis.The results showed that 1981 DEGs(1370 upregulated and 611 downregulated)were identified in the HFD group compared with the CON group.Moreover,474 DEGs(350 upregulated and 124 downregulated)were detected in the ARD group compared with the HFD group.Furthermore,GO analysis revealed that DEGs were mainly involved in the following functions:developmental process,response to an external stimulus,ion transport,alcohol binding,and plasma membrane part.Pathway analysis suggested that these DEGs were significantly enriched in bile secretion,malaria,cell adhesion molecules,retinol metabolism,the sphingolipid signaling pathway,chemical carcinogenesis,and the T cell receptor signaling pathway.In conclusion,our study demonstrated that ARD alleviated the lipid metabolism disorder caused by HLP through multiple mechanisms,which provided vital scientific evidence for further pharmacological studies of ARD.
基金supported in part by the National Natural Science Foundation of China(No.U19A2064)the Hunan Provincial Science and Technology Program(No.2019CB1007)+1 种基金the Fundamental Research Funds for the Central Universities,CSU(No.2282019SYLB004)the Fundamental Research Funds for the Central Universities of Central South University(No.2020zzts593)。
文摘Recently,the emergence of single-cell RNA-sequencing(scRNA-seq)technology makes it possible to solve biological problems at the single-cell resolution.One of the critical steps in cellular heterogeneity analysis is the cell type identification.Diverse scRNA-seq clustering methods have been proposed to partition cells into clusters.Among all the methods,hierarchical clustering and spectral clustering are the most popular approaches in the downstream clustering analysis with different preprocessing strategies such as similarity learning,dropout imputation,and dimensionality reduction.In this study,we carry out a comprehensive analysis by combining different strategies with these two categories of clustering methods on scRNA-seq datasets under different biological conditions.The analysis results show that the methods with spectral clustering tend to perform better on datasets with continuous shapes in two-dimension,while those with hierarchical clustering achieve better results on datasets with obvious boundaries between clusters in two-dimension.Motivated by this finding,a new strategy,called QRS,is developed to quantitatively evaluate the latent representative shape of a dataset to distinguish whether it has clear boundaries or not.Finally,a data-driven clustering recommendation method,called DDCR,is proposed to recommend hierarchical clustering or spectral clustering for scRNA-seq data.We perform DDCR on two typical single cell clustering methods,SC3 and RAFSIL,and the results show that DDCR recommends a more suitable downstream clustering method for different scRNA-seq datasets and obtains more robust and accurate results.
基金supported by the National Natural Science Foundation of China(Grant No.82003721)Shenzhen Science and Technology Innovation Commission(Grants No.JCYJ20210324114014039 and JCYJ20210324115800001)+4 种基金China Postdoctoral Science Foundation(Grant No.2020M683182)Guangdong Basic and Applied Basic Research Foundation(Grant No.2020A1515110549)the National Key Research and Development Program of China(Grant No.2020YFA0908000)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.ZYYCXTD-C-202002)the Sanming Project of Medicine in Shenzhen(Grant No.SZSM201612034).
文摘Background:The growing male reproductive diseases have been linked to higher exposure to certain environmental compounds such as 2,2,4,4-tetrabromodiphenyl ether(BDE47)that are widely distributed in the food chain.However,the specific underlying molecular mechanisms for BDE47-induced male reproductive toxicity are not completely understood.Methods:Here,for the first time,advanced single-cell RNA sequencing(ScRNA-seq)was employed to dissect BDE47-induced prepubertal testicular toxicity in mice from a pool of 76859 cells.Results:Our ScRNA-seq results revealed shared and heterogeneous information of differentially expressed genes,signaling pathways,transcription factors,and ligands-receptors in major testicular cell types in mice upon BDE47 treatment.Apart from disruption of hormone homeostasis,BDE47 was discovered to downregulate multiple previously unappreciated pathways such as double-strand break repair and cytokinesis pathways,indicative of their potential roles involved in BDE47-induced testicular injury.Interestingly,transcription factors analysis of ScRNA-seq results revealed that Kdm5b(lysine-specific demethylase 5B),a key transcription factor required for spermatogenesis,was downregulated in all germ cells as well as in Sertoli and telocyte cells in BDE47-treated testes of mice,suggesting its contribution to BDE47-induced impairment of spermatogenesis.Conclusions:Overall,for the first time,we established the molecular cell atlas of mice testes to define BDE47-induced prepubertal testicular toxicity using the ScRNA-seq approach,providing novel insight into our understanding of the underlying mechanisms and pathways involved in BDE47-associated testicular injury at a single-cell resolution.Our results can serve as an important resource to further dissect the potential roles of BDE47,and other relevant endocrine-disrupting chemicals,in inducing male reproductive toxicity.
文摘With the support by the National Natural Science Foundation of China,the research team directed by Prof.Tang FuChou(汤富酬)at the Biomedical Pioneering Innovation Center(BIOPIC),College of life Sciences,Peking University,and Prof.Qiao Jie(乔杰)at Peking University Third Hospital recently dissected the gene expression profiles of the four main organs of human fetal digestive tract and the adult large intestine in vivo at single-cell resolution,which was published in Nature Cell Biology(2018,20(6):721-734).The first author of the paper is associate professor Gao Shuai(高帅)at the College of Animal Science and Technology,China Agricultural University.
基金supported by the fund for National Key Research and Development Program of China(2023YFD2301203-05)the BTNYGG,China(NYHXGG,2023AA102)the Key Programs for Science and Technology Development of Shihezi City,Xinjiang Production and Construction Corps,China(2022NY01)。
文摘Verticillium dahliae causes significant losses in cotton production.To reveal the mechanism of the defense response to V.dahliae in cotton,transcriptomic analyses were performed using cotton cultivars M138(V.dahliae-resistant)and P2(V.dahliae-susceptible).The results revealed 11,076 and 6,640 differentially expressed genes(DEGs)in response to V.dahliae,respectively.The weighted gene co-expression network analysis of 4,633 transcription factors(TFs)indicated a“MEblue”module containing 654 TFs that strongly correlate with resistance to V.dahliae.Among these TFs,the ethylene response factor Ghi_A05G10166(GhERF91)was identified as a putative hub gene with a defense response against V.dahliae.A virus-induced gene silencing assay and exogenous application of ethephon showed that GhERF91 is activated by ethylene and positively regulates the response to V.dahliae exposure in cotton.This study provides fundamental transcriptome data and a putative causal gene(GhERF91)associated with resistance to V.dahliae,as well as genetic resources for breeding V.dahliae-resistant cotton.
基金supported by the China Scholarship Council(to YW)the Swedish Research Council,No.2018-02601(to MS)+7 种基金the Alzheimer Foundation,No.AF-980695(to MS)the Stockholm County Council,No.RS2020-0731(to MS)the Foundation of Old Servants(to MS)the Gun and Bertil Stohne Foundation(to MS)the?hlén Foundation,No.233055(to MS)The Swedish Fund for Research without Animal Experiments(to MS)the Swedish Dementia Foundation(to MS)the Brain foundation,No.FO2022-0131(to MS)。
文摘Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.
基金supported by funding from Lallemand Health Solution(Mirabel,QC)Alberta Milk(Edmonton,AB)+3 种基金the Saskatoon Colostrum Co.Ltd.(Saskatoon,SK)the Natural Sciences and Engineering Research Council of Canada(Ottawa,ON)supported by a Mitacs Accelerate Program from Mitacs Canada(Toronto,ON)Lallemand SAS(Blagnac,France)。
文摘Background As Holstein calves are susceptible to gastrointestinal disorders during the first week of life,understanding how intestinal immune function develops in neonatal calves is important to promote better intestinal health.Feeding probiotics in early life may contribute to host intestinal health by facilitating beneficial bacteria colonization and developing intestinal immune function.The objective of this study was to characterize the impact of early life yeast supplementation and growth on colon mucosa-attached bacteria and host immune function.Results Twenty Holstein bull calves received no supplementation(CON)or Saccharomyces cerevisiae boulardii(SCB)from birth to 5 d of life.Colon tissue biopsies were taken within 2 h of life(D0)before the first colostrum feeding and 3 h after the morning feeding at d 5 of age(D5)to analyze mucosa-attached bacteria and colon transcriptome.Metagenome sequencing showed that there was no difference inαandβdiversity of mucosa-attached bacteria between day and treatment,but bacteria related to diarrhea were more abundant in the colon mucosa on D0 compared to D5.In addition,q PCR indicated that the absolute abundance of Escherichia coli(E.coli)decreased in the colon mucosa on D5 compared to D0;however,that of Bifidobacterium,Lactobacillus,and Faecalibacterium prausnitzii,which could competitively exclude E.coli,increased in the colon mucosa on D5 compared to D0.RNA-sequencing showed that there were no differentially expressed genes between CON and SCB,but suggested that pathways related to viral infection such as“Interferon Signaling”were activated in the colon mucosa of D5 compared to D0.Conclusions Growth affected mucosa-attached bacteria and host immune function in the colon mucosa during the first 5 d of life in dairy calves independently of SCB supplementation.During early life,opportunistic pathogens may decrease due to intestinal environmental changes by beneficial bacteria and/or host immune function.Predicted activation of immune function-related pathways may be the result of host immune function development or suggest other antigens in the intestine during early life.Further studies focusing on the other antigens and host immune function in the colon mucosa are required to better understand intestinal immune function development.
基金supported by the earmarked fund for CARS,China(CARS-42)the earmarked fund for Jiangsu Agricultural Industry Technology System,China(JATS(2022)331)the Jiangsu Key Research and Development Program,China(BE2021332)。
文摘The Chinese crested duck is a unique duck breed having a bulbous feather shape on its duck head.However,the mechanisms involved in its formation and development are unclear.In the present study,RNA sequencing analysis was performed on the crested tissues of 6 Chinese crested ducks and the scalp tissues of 6 cherry valley ducks(CVs)from 2 developmental stages.This study identified 261 differentially expressed genes(DEGs),122 upregulated and 139 downregulated,in the E28 stage and 361 DEGs,154 upregulated and 207 downregulated in the D42 stage between CC and CV ducks.The subsequent results of weighted gene co-expression network analysis(WGCNA)revealed that the turquoise and cyan modules were associated with the crest trait in the D42 stage,meanwhile,the green,brown,and pink modules were associated with the crest trait in the E28 stage.Venn analysis of the DEGs and WGCNA showed that 145 and 45 genes are associated between the D42 and E28 stages,respectively.The expression of WNT16,BMP2,SLC35F2,SLC6A15,APOBEC2,ABHD6,TNNC2,MYL1,and TNNI2 were verified by real-time quantitative PCR.This study provides an approach to reveal the molecular mechanisms underlying the crested trait development.
基金Supported by National Natural Science Foundation of China,No.82260133 and No.82370661the Academic and Technical Leader of major disciplines in Jiangxi Province,No.20225BCJ23021+2 种基金the Jiangxi Medicine Academy of Nutrition and Health Management,No.2022-PYXM-01the Natural Science Foundation of Jiangxi Province,No.20224ACB216004the Technological Innovation Team Cultivation Project of the First Affiliated Hospital of Nanchang University,No.YFYKCTDPY202202.
文摘BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.
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.
文摘Mucin genes are the main component of mucus. The sea anemone species, Aulactinia veratra (Phylum Cnidaria) contains different types of mucin genes. In the intertidal zone, A. veratra is found to be exposed to air during the low tide and produces large quantities of mucus as an external covering. The relation between low tide and mucus secretion is still unclear, and what is the role of mucin during arial exposure is not yet investigated. This study hypothesised that the mucin genes in A. veratra would have significantly high expression in response to aerial exposure. Therefore, the aim of current study was to examine and analyses the response of A. veratra mucins in response to an experiment involving three hours of aerial exposure. To achieve this, aim the RNA-sequencing and bioinformatics analyses were used to examine the expression profile of A. veratra mucin genes in response to aerial exposure. The generated results have shown that, Mucin4-like and mucin5B-like were up-regulated in response to the three hours of aerial exposure in A. veratra. This finding shows a significant role of mucin5B-like and mucin4-like genes in response to air stress at low tide. The data generated from this study could be used in conjunction with future mucin gene studies of sea anemones and other cnidarians to compare A. veratra mucin gene expression results across time, and to extend our understanding of mucin stress response in this phylum.
基金supported by the National Natural Science Foundation of China(32200688,92068106,U20A2015,32211530050)Guangdong Basic and Applied Basic Research Foundation(2021B1515120075,2021A1515110180)Science and Technology Program of Guangzhou(202201010408,202201011037)。
文摘Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis stages.To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver fibrosis.Integrative analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial cells.Moreover,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these processes.These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver fibrosis.Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.
文摘Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion(II/R)injury by single-cell RNA sequencing.For enterocyte cells,11 subclusters were found,in which enterocyte cluster 1(EC1),enterocyte cluster 3(EC3),and enterocyte cluster 8(EC8)were newly discovered cells in ischemia 45 min/reperfusion 720 min(I 45 min/R 720 min)group.EC1 and EC3 played roles in digestion and absorption,and EC8 played a role in cell junctions.For TA cells,after ischemia 45 min/reperfusion 90 min(I 45 min/R 90 min),many TA cells at the stage of proliferation were identified.For Paneth cells,Paneth cluster 3 was observed in the resting state of normal jejunum.After I 45 min/R 90 min,three new subsets were found,in which Paneth cluster 1 had good antigen presentation activity.The main functions of goblet cells were to synthesize and secrete mucus,and a novel subcluster(goblet cluster 5)with highly proliferative ability was discovered in I 45 min/R 90 min group.As a major part of immune system,the changes in T cells with important roles were clarified.Notably,enterocyte cells secreted Guca2b to interact with Gucy2c receptor on the membranes of stem cells,TA cells,Paneth cells,and goblet cells to elicit intercellular communication.One marker known as glutathione S-transferase mu 3(GSTM3)affected intestinal mucosal barrier function by adjusting mitogen-activated protein kinases(MAPK)signaling during II/R injury.The data on the heterogeneity of intestinal cells,cellular communication and the mechanism of GSTM3 provide a cellular basis for treating II/R injury.
文摘Over the past decade,the advent of single cell RNA-sequencing has revolutionized the approach in cellular transcriptomics research.The current technology offers an unbiased platform to understand how genotype correlates to phenotype.Single-cell omics applications in gastrointestinal(GI)research namely inflammatory bowel disease(IBD)has become popular in the last few years with multiple publications as single-cell omics techniques can be applied directly to the target organ,the GI tract at the tissue level.Through examination of mucosal tissue and peripheral blood in IBD,the recent boom in single cell research has identified a myriad of key immune players from enterocytes to tissue resident memory T cells,and explored functional heterogeneity within cellular subsets previously unreported.As we begin to unravel the complex mucosal immune system in states of health and disease like IBD,the power of exploration through single-cell omics can change our approach to translational research.As novel techniques evolve through multiplexing single-cell omics and spatial transcriptomics come to the forefront,we can begin to fully comprehend the disease IBD and better design targets of treatment.In addition,hopefully these techniques can ultimately begin to identify biomarkers of therapeutic response and answer clinically relevant questions in how to tailor individual therapy to patients through personalized medicine.
