As the major cell precursors in osteogenesis, mesenchymal stem cells(MSCs) are indispensable for bone homeostasis and development. However, the primary mechanisms regulating osteogenic differentiation are controversia...As the major cell precursors in osteogenesis, mesenchymal stem cells(MSCs) are indispensable for bone homeostasis and development. However, the primary mechanisms regulating osteogenic differentiation are controversial. Composed of multiple constituent enhancers, super enhancers(SEs) are powerful cis-regulatory elements that identify genes that ensure sequential differentiation. The present study demonstrated that SEs were indispensable for MSC osteogenesis and involved in osteoporosis development. Through integrated analysis, we identified the most common SE-targeted and osteoporosis-related osteogenic gene,ZBTB16. ZBTB16, positively regulated by SEs, promoted MSC osteogenesis but was expressed at lower levels in osteoporosis.Mechanistically, SEs recruited bromodomain containing 4(BRD4) at the site of ZBTB16, which then bound to RNA polymerase IIassociated protein 2(RPAP2) that transported RNA polymerase Ⅱ(POL Ⅱ) into the nucleus. The subsequent synergistic regulation of POL Ⅱ carboxyterminal domain(CTD) phosphorylation by BRD4 and RPAP2 initiated ZBTB16 transcriptional elongation, which facilitated MSC osteogenesis via the key osteogenic transcription factor SP7. Bone-targeting ZBTB16 overexpression had a therapeutic effect on the decreased bone density and remodeling capacity of Brd4^(fl/fl)Prx1-cre mice and osteoporosis(OP) models.Therefore, our study shows that SEs orchestrate the osteogenesis of MSCs by targeting ZBTB16 expression, which provides an attractive focus and therapeutic target for osteoporosis.展开更多
Inflammation can initiate osteolysis,which is the breakdown of bone by fully developed osteoclasts.The com-pound Oleandrin is recognized for its effects against inflammation and tumors.Our objective was to examine the...Inflammation can initiate osteolysis,which is the breakdown of bone by fully developed osteoclasts.The com-pound Oleandrin is recognized for its effects against inflammation and tumors.Our objective was to examine the effects of Oleandrin on osteoclastogenesis and osteolysis,both in vitro and in vivo.In vitro,the impact of Oleandrin on osteoclastogenesis was assessed using CCK-8 assays,TRAP staining,and bone resorption assays.Ad-ditionally,a mouse model of osteolysis caused by LPS injection into the calvaria was used to conduct an in vivo investigation,examining bone histomorphology,histology,and immunohistochemistry.In vitro,concentrations of 5 nM and 10 nM of Oleandrin were found to be non-cytotoxic based on the results obtained.In vitro,Olean-drin hindered the osteoclastogenesis and bone resorption induced by RANKL.Oleandrin successfully inhibited the phosphorylation of NF-κB p65 and PI3K p85 in osteolytic tissue,thereby suppressing LPS-induced inflammatory osteolysis in mice calvaria during the in vivo study.Furthermore,the Oleandrin-treated group exhibited a note-worthy decrease in the expression level of NFATc1,which is a crucial controller of osteoclastogenesis.To sum up,our discoveries indicate that Oleandrin could hinder osteoclastogenesis and bone resorption,thereby having the ability to suppress inflammation-induced osteolysis.The underlying mechanism involves the NF-κB/PI3K pathway and inhibition of NFATc1 activation.Therefore,the findings suggest that Oleandrin holds potential as a therapeutic remedy for osteolytic ailments.展开更多
Lignocellulosic biomass such as plants and agricultural waste are ideal to tackle the current energy crisis and energy-related environmental issues.Carbon-rich lignin is abundant in lignocellulosic biomass,whose high-...Lignocellulosic biomass such as plants and agricultural waste are ideal to tackle the current energy crisis and energy-related environmental issues.Carbon-rich lignin is abundant in lignocellulosic biomass,whose high-value transformation and utilization has been the most urgent problem to be solved.Herein,we propose a method for the preparation of porous carbon from lignin employing an H_(3)PO_(4)-assisted hydrothermal method.We characterize the as-prepared lignin-derived porous carbon and investigate its potential for energy storage.After assisted hydrothermal treatment followed by carbonization at 800℃,the lignin-derived porous carbon displays a high specific capacitance(223.6 F·g^(–1) at 0.1 A·g^(–1))and excellent cycling ability with good capacitance retention.In this present study,the resultant lignin-derived porous carbon was used as the electrode of a supercapacitor,illustrating yet another potential high-value use for lignin,namely as a candidate for the sustainable fabrication of main supercapacitor components.展开更多
Dear Editor,The placenta connecting the fetus to the matermal uterus provides material exchange and an immune-tolerant environment for the embryo in all eutherian mammals(Shao et al.,2022).The representative mouse pla...Dear Editor,The placenta connecting the fetus to the matermal uterus provides material exchange and an immune-tolerant environment for the embryo in all eutherian mammals(Shao et al.,2022).The representative mouse placenta displays a multilayered structure with distinct characteristics and functions,including the matermal decidua,junctional zone,and labyrinth layer(Marsh and Blelloch,2020).The decidua,which is thought to be derived from the matermal endometrium(and further undergoes decidualization),provides an anchor for fetal trophoblast invasion.The junctional zone predominantly contains spongiotrophoblasts(SpT),glycogen trophoblasts(GlyT),and trophoblast giant cells(TGCs).The labyrinth is the innermost two-layer structure,which mainly consists of syncytiotrophoblast cells(SynTI and SynTII),sinusoidal TGCs(S-TGCs),and fetal endothelial cells(Simmons and Cross,2005).展开更多
The naturally occurring prokaryotic CRISPR-Cas systems provide valuable resources for the development of new genome-editing tools.However,the majority of prokaryotic Cas nucleases exhibit poor editing efficiency in ma...The naturally occurring prokaryotic CRISPR-Cas systems provide valuable resources for the development of new genome-editing tools.However,the majority of prokaryotic Cas nucleases exhibit poor editing efficiency in mammalian cells,which significantly limits their utility.Here,we have developed a method termed Improving Editing Activity by Synergistic Engineering(MIDAS).This method exerts a synergistic effect to improve mammalian genome-editing efficiency of a wide range of CRISPR-Cas systems by enhancing the interactions of Cas nuclease with the protospacer adjacent motif(PAM)and the single-stranded DNA(ssDNA)substrate in the catalytic pocket simultaneously.MIDAS robustly and significantly increased the gene-editing efficiency of Cas12i,Cas12b,and CasX in human cells.Notably,a Cas12i variant,Cas12iMax,exhibited robust activity with a very broad PAM range(NTNN,NNTN,NAAN,and NCAN)and higher efficiency than the current widely used Cas nucleases.A high-fidelity version of Cas12iMax(Cas12iHiFi)has been further engineered to minimize off-target effects.Our work provides an expandable and efficacious method for engineering Cas nucleases for robust mammalian genome editing.展开更多
Glutaric aciduria type I(GA-I)is an autosomal recessive genetic disorder caused by a deficiency in glutaryl-CoA dehydrogenase(GCDH).Patients who do not receive proper treatment may die from acute encephalopathic crisi...Glutaric aciduria type I(GA-I)is an autosomal recessive genetic disorder caused by a deficiency in glutaryl-CoA dehydrogenase(GCDH).Patients who do not receive proper treatment may die from acute encephalopathic crisis.Current treatments for GA-I include a low-lysine diet combined with oral supplementation of L-carnitine.A mouse model of Gcdh^(c.422_428del/c.422_428del)(Gcdh^(−/−))was generated in our laboratory using CRISPR/Cas9.Gcdh^(−/−)mice had significantly higher levels of glutaric acid(GA)in the plasma,liver,and brain than those in wild-type C57BL/6 mice.When given a high-protein diet(HPD)for two days,approximately 60%of Gcdh^(−/−)mice did not survive the metabolic stress.To evaluate whether GCDH gene replacement therapy could be used to provide sustained treatment for patients with GA-1,we prepared a recombinant adeno-associated virus(rAAV)carrying a human GCDH expression cassette and injected it into Gcdh^(−/−)neonates for a proof-of-concept(PoC)study.Our study demonstrated that delivering rAAV to the central nervous system(CNS),but not the peripheral system,significantly increased the survival rate under HPD exposure.Our study also demonstrated that rAAVPHP.eB mediated a higher efficiency than that of rAAV9 in increasing the survival rate.Surviving mice showed dose-dependent GCDH protein expression in the CNS and downregulation of GA levels.Our study demonstrated that AAV-based gene replacement therapy was effective for GA-I treatment and provided a feasible solution for this unmet medical need.展开更多
Dear editor.The remarkably diversified CRISPR-Cas systems in nature have provided unlimited valuable resources to develop genome editing tools that are revolutionizing the fields of biotechnology and medicine.However,...Dear editor.The remarkably diversified CRISPR-Cas systems in nature have provided unlimited valuable resources to develop genome editing tools that are revolutionizing the fields of biotechnology and medicine.However,due to their microbial origin,the activity of most naturally occurring CRISPR-Cas nucleases is relatively poor in mammalian cells(Ran et al.,2015).Thus,improving the mammalian genome editing efficiency becomes the priority for harnessing more CRISPRCas systems for widespread applications.Rational protein engineering serves as a powerful approach to enhance the catalytic activity of enzymes.Whereas,this approach largely relies on proteinic three-dimension(3D)structure information as guide for design.The fact is that of the large numbers of the CRISPR-Cas systems discovered in recent years,only a small number of them with the 3D structures were reported.To bypass this limitation,here,we report an efficient and simple strategy for rational engineering of Cas nucleases without the need of 3D structure information and successfully optimized nucleases from Cas9 and Cas12 families.展开更多
1.Background.Polymethyl methacrylate(PMMA)bone cement has been widely used in orthopedic clinics for over 70 years.In 1952 and 1953,Kiaer and Haboush reported their work on the use of PMMA cement to achieve bone adher...1.Background.Polymethyl methacrylate(PMMA)bone cement has been widely used in orthopedic clinics for over 70 years.In 1952 and 1953,Kiaer and Haboush reported their work on the use of PMMA cement to achieve bone adherence to prostheses in femoral head replacement[1,2],.In 1987,Galibert et al.first reported the use of PMMA cement in spinal surgery for vertebroplasty(PVP)to treat vertebral hemangiomas[3].By 2002,approximately 38,000 vertebroplasties and 16,000 kyphoplasties were performed in the United States[4].展开更多
Diploidy is the typical genomic mode in all mammals.Haploid stem cells are artificial cell lines experimentally derived in vitro in the form of different types of stem cells,which combine the characteristics of haploi...Diploidy is the typical genomic mode in all mammals.Haploid stem cells are artificial cell lines experimentally derived in vitro in the form of different types of stem cells,which combine the characteristics of haploidy with a broad developmental potential and open the possibility to uncover biological mysteries at a genomic scale.To date,a multitude of haploid stem cell types from mouse,rat,monkey and humans have been derived,as more are in development.They have been applied in high-throughput genetic screens and mammalian assisted reproduction.Here,we review the generation,unique properties and broad applications of these remarkable cells.展开更多
Epigenetic reprogramming of somatic cells into induced pluripotent stem cells （iPSCs） by overexpression of defined factors holds great promise for disease modeling and regen- erative medicine （Takahashi and Yamanak...Epigenetic reprogramming of somatic cells into induced pluripotent stem cells （iPSCs） by overexpression of defined factors holds great promise for disease modeling and regen- erative medicine （Takahashi and Yamanaka, 2006; Robinton and Daley, 2012）. However, the stochastic reprogramming process often results in variable pluripotency levels of iPSC lines as measured by their in vivo developmental potential, which poses a huge challenge to the applications of high quality iPSCs （Hanna et al., 2010）. The activation status of an imprinted Dlkl-Dio3 region has been identified as a molecular marker for pluripotency （Liu et al., 2010; Stadtfeld et al.,展开更多
基金supported by the National Distinguished Veteran TCM Expert Professor Wanlin Wang Inheritance Workshop Construction Project{National Chinese Medicine People Education Letter[2019]No.41(CZ0175)}Health Commission of Henan Province National TCM Clinical Research Base Scientific Research Special Project(2021JDZY018)Health Commission of Henan Province National TCM Clinical Research Base Reward Project(2022JDZX086)。
基金supported by the National Natural Science Foundation of China [82172385 to H.S., 82172349 to Y.W.]the Key-Area Research and Development Program of Guangdong Province [2019B020236001 to H.S.]+3 种基金the Shenzhen Key Medical Discipline Construction Fund [ZDSYS20190902092851024 to H.S.]the Natural Science Foundation of Guangdong Province [2020A1515010097 to Z.X.]the Shenzhen Outstanding Science and Technology Innovation Talents-Outstanding Youth Fund project [RCYX20210706092106042 to Z.X.]Funding for open access charge:Shenzhen Key Medical Discipline Construction Fund。
文摘As the major cell precursors in osteogenesis, mesenchymal stem cells(MSCs) are indispensable for bone homeostasis and development. However, the primary mechanisms regulating osteogenic differentiation are controversial. Composed of multiple constituent enhancers, super enhancers(SEs) are powerful cis-regulatory elements that identify genes that ensure sequential differentiation. The present study demonstrated that SEs were indispensable for MSC osteogenesis and involved in osteoporosis development. Through integrated analysis, we identified the most common SE-targeted and osteoporosis-related osteogenic gene,ZBTB16. ZBTB16, positively regulated by SEs, promoted MSC osteogenesis but was expressed at lower levels in osteoporosis.Mechanistically, SEs recruited bromodomain containing 4(BRD4) at the site of ZBTB16, which then bound to RNA polymerase IIassociated protein 2(RPAP2) that transported RNA polymerase Ⅱ(POL Ⅱ) into the nucleus. The subsequent synergistic regulation of POL Ⅱ carboxyterminal domain(CTD) phosphorylation by BRD4 and RPAP2 initiated ZBTB16 transcriptional elongation, which facilitated MSC osteogenesis via the key osteogenic transcription factor SP7. Bone-targeting ZBTB16 overexpression had a therapeutic effect on the decreased bone density and remodeling capacity of Brd4^(fl/fl)Prx1-cre mice and osteoporosis(OP) models.Therefore, our study shows that SEs orchestrate the osteogenesis of MSCs by targeting ZBTB16 expression, which provides an attractive focus and therapeutic target for osteoporosis.
基金by the Inheritance Studio of Professor Wang Wanlin,the National Famous Chinese Medicine Expert{41st Letter of Education ofTCM in 2019(CZ0175)}Special Research Project of Clinical Research Base of TCM Administration of Henan Province(2017JDZX017)Special Research Project of TCM Research of Henan Province(2018ZY2089).
基金National Natural Science Foundation of China(82272165)Shanghai Municipal Commission of Health and Family Planning’s Science and Research Fund(202040141)+2 种基金Shanghai Municipality Science and Technology Commission(20ZR1451800,22ZR1457200)Shanghai Municipal Health Commission(2022YQ006)Shanghai Tongren Hospital(TRKYRC-xx202203).
文摘Inflammation can initiate osteolysis,which is the breakdown of bone by fully developed osteoclasts.The com-pound Oleandrin is recognized for its effects against inflammation and tumors.Our objective was to examine the effects of Oleandrin on osteoclastogenesis and osteolysis,both in vitro and in vivo.In vitro,the impact of Oleandrin on osteoclastogenesis was assessed using CCK-8 assays,TRAP staining,and bone resorption assays.Ad-ditionally,a mouse model of osteolysis caused by LPS injection into the calvaria was used to conduct an in vivo investigation,examining bone histomorphology,histology,and immunohistochemistry.In vitro,concentrations of 5 nM and 10 nM of Oleandrin were found to be non-cytotoxic based on the results obtained.In vitro,Olean-drin hindered the osteoclastogenesis and bone resorption induced by RANKL.Oleandrin successfully inhibited the phosphorylation of NF-κB p65 and PI3K p85 in osteolytic tissue,thereby suppressing LPS-induced inflammatory osteolysis in mice calvaria during the in vivo study.Furthermore,the Oleandrin-treated group exhibited a note-worthy decrease in the expression level of NFATc1,which is a crucial controller of osteoclastogenesis.To sum up,our discoveries indicate that Oleandrin could hinder osteoclastogenesis and bone resorption,thereby having the ability to suppress inflammation-induced osteolysis.The underlying mechanism involves the NF-κB/PI3K pathway and inhibition of NFATc1 activation.Therefore,the findings suggest that Oleandrin holds potential as a therapeutic remedy for osteolytic ailments.
基金The authors wish to express their gratitude for the financial support from the National Science Foundation for Post-doctoral Scientists of China(Grant No.2019M651050)Guangxi Key Laboratory of Clean Pulp&Papermaking and Pollution Control,College of Light Industry and Food Engineering,Guangxi University(Grant No.2019KF32).
文摘Lignocellulosic biomass such as plants and agricultural waste are ideal to tackle the current energy crisis and energy-related environmental issues.Carbon-rich lignin is abundant in lignocellulosic biomass,whose high-value transformation and utilization has been the most urgent problem to be solved.Herein,we propose a method for the preparation of porous carbon from lignin employing an H_(3)PO_(4)-assisted hydrothermal method.We characterize the as-prepared lignin-derived porous carbon and investigate its potential for energy storage.After assisted hydrothermal treatment followed by carbonization at 800℃,the lignin-derived porous carbon displays a high specific capacitance(223.6 F·g^(–1) at 0.1 A·g^(–1))and excellent cycling ability with good capacitance retention.In this present study,the resultant lignin-derived porous carbon was used as the electrode of a supercapacitor,illustrating yet another potential high-value use for lignin,namely as a candidate for the sustainable fabrication of main supercapacitor components.
基金supported by the National Key Research and Development Program of China(2018YFE0201100 to Lw.,2019YFA0110901 to G.F,2022YFA1104101 to GF,2022YFA1104300 to CL.)the Youth Innovation Promotion Association,CAS(2019084 to GF),informatization Plan of Chinese Academy of Sciences(CAS-Wx20215F-0101 to GF)the National Natural Science Foundation of China(31972895 toLw).
文摘Dear Editor,The placenta connecting the fetus to the matermal uterus provides material exchange and an immune-tolerant environment for the embryo in all eutherian mammals(Shao et al.,2022).The representative mouse placenta displays a multilayered structure with distinct characteristics and functions,including the matermal decidua,junctional zone,and labyrinth layer(Marsh and Blelloch,2020).The decidua,which is thought to be derived from the matermal endometrium(and further undergoes decidualization),provides an anchor for fetal trophoblast invasion.The junctional zone predominantly contains spongiotrophoblasts(SpT),glycogen trophoblasts(GlyT),and trophoblast giant cells(TGCs).The labyrinth is the innermost two-layer structure,which mainly consists of syncytiotrophoblast cells(SynTI and SynTII),sinusoidal TGCs(S-TGCs),and fetal endothelial cells(Simmons and Cross,2005).
基金supported by the National Key Research and Development Program(2019YFA0110800 and 2020YFA0707900 to W.L.and 2018YFA0108400 and 2019YFA0903800 to Q.Z.)the Strategic Priority Research Programof the Chinese Academy of Sciences(XDA16030403 to W.L.)+1 种基金the National Natural Science Foundation of China(31621004 to Q.Z.and W.L.)and the CAS Project for Young Scientists in Basic Research(YSBR-012 to W.L.).
文摘The naturally occurring prokaryotic CRISPR-Cas systems provide valuable resources for the development of new genome-editing tools.However,the majority of prokaryotic Cas nucleases exhibit poor editing efficiency in mammalian cells,which significantly limits their utility.Here,we have developed a method termed Improving Editing Activity by Synergistic Engineering(MIDAS).This method exerts a synergistic effect to improve mammalian genome-editing efficiency of a wide range of CRISPR-Cas systems by enhancing the interactions of Cas nuclease with the protospacer adjacent motif(PAM)and the single-stranded DNA(ssDNA)substrate in the catalytic pocket simultaneously.MIDAS robustly and significantly increased the gene-editing efficiency of Cas12i,Cas12b,and CasX in human cells.Notably,a Cas12i variant,Cas12iMax,exhibited robust activity with a very broad PAM range(NTNN,NNTN,NAAN,and NCAN)and higher efficiency than the current widely used Cas nucleases.A high-fidelity version of Cas12iMax(Cas12iHiFi)has been further engineered to minimize off-target effects.Our work provides an expandable and efficacious method for engineering Cas nucleases for robust mammalian genome editing.
基金the National Key Research and Development Program(2019YFA0110800 and 2020YFA0707900 to W.L.,and 2018YFA0108400 and 2019YFA0903800 to Q.Z.)Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030403 to W.L.)+1 种基金National Natural Science Foundation of China(31621004 to Q.Z.and W.L.)CAS Project for Young Scientists in Basic Research(YSBR-012 to W.L.).
文摘Glutaric aciduria type I(GA-I)is an autosomal recessive genetic disorder caused by a deficiency in glutaryl-CoA dehydrogenase(GCDH).Patients who do not receive proper treatment may die from acute encephalopathic crisis.Current treatments for GA-I include a low-lysine diet combined with oral supplementation of L-carnitine.A mouse model of Gcdh^(c.422_428del/c.422_428del)(Gcdh^(−/−))was generated in our laboratory using CRISPR/Cas9.Gcdh^(−/−)mice had significantly higher levels of glutaric acid(GA)in the plasma,liver,and brain than those in wild-type C57BL/6 mice.When given a high-protein diet(HPD)for two days,approximately 60%of Gcdh^(−/−)mice did not survive the metabolic stress.To evaluate whether GCDH gene replacement therapy could be used to provide sustained treatment for patients with GA-1,we prepared a recombinant adeno-associated virus(rAAV)carrying a human GCDH expression cassette and injected it into Gcdh^(−/−)neonates for a proof-of-concept(PoC)study.Our study demonstrated that delivering rAAV to the central nervous system(CNS),but not the peripheral system,significantly increased the survival rate under HPD exposure.Our study also demonstrated that rAAVPHP.eB mediated a higher efficiency than that of rAAV9 in increasing the survival rate.Surviving mice showed dose-dependent GCDH protein expression in the CNS and downregulation of GA levels.Our study demonstrated that AAV-based gene replacement therapy was effective for GA-I treatment and provided a feasible solution for this unmet medical need.
基金supported by the National Key Research and Development Program(2020YFA0707900,2018YFE0201100,2019YFA0110800 to W.L.,2018YFA0108400,2019YFA0903800 to Q.Z.)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030403 to W.L.)+1 种基金the National Natural Science Foundation of China(31621004 to Q.Z.and W.L.)the CAS Project for Young Scientists in Basic Research(YSBR-012 to W.L.)。
文摘Dear editor.The remarkably diversified CRISPR-Cas systems in nature have provided unlimited valuable resources to develop genome editing tools that are revolutionizing the fields of biotechnology and medicine.However,due to their microbial origin,the activity of most naturally occurring CRISPR-Cas nucleases is relatively poor in mammalian cells(Ran et al.,2015).Thus,improving the mammalian genome editing efficiency becomes the priority for harnessing more CRISPRCas systems for widespread applications.Rational protein engineering serves as a powerful approach to enhance the catalytic activity of enzymes.Whereas,this approach largely relies on proteinic three-dimension(3D)structure information as guide for design.The fact is that of the large numbers of the CRISPR-Cas systems discovered in recent years,only a small number of them with the 3D structures were reported.To bypass this limitation,here,we report an efficient and simple strategy for rational engineering of Cas nucleases without the need of 3D structure information and successfully optimized nucleases from Cas9 and Cas12 families.
基金supported by the National Natural Science Foundation of China(No.82272165)the Shanghai Committee of Science and Technology(No.20ZR1451800)+1 种基金the Municipal Health Commission Fundation of Shanghai(No.202040141)the Outstanding Youth Foundation Project of Tongren(No.2020SHTRYC02)。
文摘1.Background.Polymethyl methacrylate(PMMA)bone cement has been widely used in orthopedic clinics for over 70 years.In 1952 and 1953,Kiaer and Haboush reported their work on the use of PMMA cement to achieve bone adherence to prostheses in femoral head replacement[1,2],.In 1987,Galibert et al.first reported the use of PMMA cement in spinal surgery for vertebroplasty(PVP)to treat vertebral hemangiomas[3].By 2002,approximately 38,000 vertebroplasties and 16,000 kyphoplasties were performed in the United States[4].
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA16030400)the National Basic Research Program of China(Grant No.2014CB964800)+2 种基金the National Natural Science Foundation of China(Grant Nos.31621004,31422038)the National Key Research and Development Program(Grant No.2017YFA0103803)CAS Key Projects(Grant No.QYZDY-SSWSMC022,QYZDB-SSW-SMC002).
文摘Diploidy is the typical genomic mode in all mammals.Haploid stem cells are artificial cell lines experimentally derived in vitro in the form of different types of stem cells,which combine the characteristics of haploidy with a broad developmental potential and open the possibility to uncover biological mysteries at a genomic scale.To date,a multitude of haploid stem cell types from mouse,rat,monkey and humans have been derived,as more are in development.They have been applied in high-throughput genetic screens and mammalian assisted reproduction.Here,we review the generation,unique properties and broad applications of these remarkable cells.
基金supported by the grants from the "Strategic Priority Research Program" of the Chinese Academy of Sciences (No. XDA01020100 to Q.Z.)the China National Basic Research Program (No. 2012CBA01300 to Q.Z.)the National Science Foundation of China (No. 91319308 to Q.Z.,31201105 to L.L. and 31371516 to W.L.)
文摘Epigenetic reprogramming of somatic cells into induced pluripotent stem cells （iPSCs） by overexpression of defined factors holds great promise for disease modeling and regen- erative medicine （Takahashi and Yamanaka, 2006; Robinton and Daley, 2012）. However, the stochastic reprogramming process often results in variable pluripotency levels of iPSC lines as measured by their in vivo developmental potential, which poses a huge challenge to the applications of high quality iPSCs （Hanna et al., 2010）. The activation status of an imprinted Dlkl-Dio3 region has been identified as a molecular marker for pluripotency （Liu et al., 2010; Stadtfeld et al.,
