With the development of high-throughput sequencing technology in the post-genomic era, researchers have concentrated their efforts on elucidating the relationships between genes and their corresponding functions. Rece...With the development of high-throughput sequencing technology in the post-genomic era, researchers have concentrated their efforts on elucidating the relationships between genes and their corresponding functions. Recently, important progress has been achieved in the generation of genetically modified mice based on CRISPR/Cas9 and haploid embryonic stem cell （haESC） approaches, which provide new platforms for gene function analysis, human disease modeling, and gene therapy. Here, we review the CRISPR/Cas9 and haESC technology for the generation of genetically modified mice and discuss the key challenges in the application of these approaches.展开更多
Identification of the function of all genes in the mammalian genome is critical in understanding basic mechanisms of biology.However,the diploidy of mammalian somatic cells has greatly hindered efforts to elucidate th...Identification of the function of all genes in the mammalian genome is critical in understanding basic mechanisms of biology.However,the diploidy of mammalian somatic cells has greatly hindered efforts to elucidate the gene function in numerous biological processes by mutagenesis-based genetic approaches.Recently,mouse haploid embryonic stem(haES)cells have been successfully isolated from parthenogenetic and androgenetic embryos,providing an ideal tool for genetic analyses.In these studies,mouse haES cells have already shown that they could be used in cell-based forward or reverse genetic screenings and in generating gene-targeting via homologous recombination.In particular,haES cells from androgenetic embryos can be employed as novel,renewable form of fertilization agent for yielding live-born mice via injection into oocytes,thus showing the possibility that genetic analysis can be extended from cellular level to organism level.展开更多
Investigating the development toxicity of perfuorinated iodine alkanes(PFIs)is critical,given their estrogenic effects through binding with estrogen receptors(ERs).In the present study,two PFIs,including dodecafuoro-1...Investigating the development toxicity of perfuorinated iodine alkanes(PFIs)is critical,given their estrogenic effects through binding with estrogen receptors(ERs).In the present study,two PFIs,including dodecafuoro-1,6-diiodohexane(PFHx DI)and tridecafuorohexyl iodide(PFHx I),with binding preference to ERαand ERβ,respectively,were selected to evaluate their effects on proliferation and differentiation of the mouse embryonic stem cells(m ESCs).The results revealed that,similar to E_(2),50μmol/L PFHx DI accelerated the cell proliferation of the m ESCs.The PFI stimulation at the exposure concentrations of 2–50μmol/L promoted the differentiation of the m ESCs as characterized by the upregulation of differentiation-related biomarkers(i.e.,Otx2 and Dnmt3β)and downregulation of pluripotency genes(i.e.,Oct4,Nanog,Sox2,Prdm14 and Rex1).Comparatively,PFHx DI exhibited higher induction effect on the differentiation of the m ESCs than did PFHx I.The tests on ER signaling indicated that both PFI compounds induced exposure concentration-dependent expressions of ER signaling-related biomarkers(i.e.,ERα,ERβand Caveolin-1)in the m ESCs,and the downstream ER responsive genes(i.e.,c-fos,c-myc and c-jun)well responded to PFHx I stimulation.The role of ER in PFI-induced effects on the m ESCs was further validated by the antagonistic experiments using an ER inhibitor(ICI).The findings demonstrated that PFIs triggered ER signaling,and perturbed the differentiation program of the m ESCs,causing the potential health risk during early stage of development.展开更多
The adverse effects of environmental pollution on our well-being have been intensively studied with many in vitro and in vivo systems. In our group, we focus on stem cell toxicology due to the multitude of embryonic s...The adverse effects of environmental pollution on our well-being have been intensively studied with many in vitro and in vivo systems. In our group, we focus on stem cell toxicology due to the multitude of embryonic stem cell（ESC） properties which can be exerted in toxicity assays. In fact, ESCs can differentiate in culture to mimic embryonic development in vivo, or specifically to virtually any kind of somatic cells. Here, we used the toxicant Bisphenol A（BPA）, a chemical known as a hazard to infants and children, and showed that our stem cell toxicology system was able to efficiently recapitulate most of the toxic effects of BPA previously detected by in vitro system or animal tests. More precisely, we demonstrated that BPA affected the proper specification of germ layers during our in vitro mimicking of the embryonic development, as well as the establishment of neural ectoderm and neural progenitor cells.展开更多
There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is ...There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is limited information available on their effects on neural development（Betts,2010;US EPA,2015）.展开更多
The self-renewal and pluripotency of embryonic stem cells (ESCs) is regulated by a network, which consists of a series of cell factors in microenviroments, a chain of transcription factors and certain signal conductio...The self-renewal and pluripotency of embryonic stem cells (ESCs) is regulated by a network, which consists of a series of cell factors in microenviroments, a chain of transcription factors and certain signal conduction pathways. This article reviews recent progress in this field to elucidate the mecha-nism involved.展开更多
Embryonic stem cells (ESCs), which are isolated from the inner cell mass of the blastocyst stage embryo, have the potential to give rise to an entire organism and to generate every body cell type. Much improvement has...Embryonic stem cells (ESCs), which are isolated from the inner cell mass of the blastocyst stage embryo, have the potential to give rise to an entire organism and to generate every body cell type. Much improvement has been made in the field of induction and differentia-tion of ESCs during the last two years, such as the ESCs differentiation into germ cells (2003) and the cloning of human ESCs (2004), both of which were chosen respectively as one of the top ten achievements evaluated by academic journals. Great attention was also paid to the research of the new genes which could maintain ESCs in the undifferentiated state and the research of the induction and differentiation of ESCs.展开更多
Progress of cell therapy for muscular dystrophies is slow. Although there are clinical trials of myoblast delivery, the result is not satisfactory. However, human stem cell especially induced pluripotent stem cells （...Progress of cell therapy for muscular dystrophies is slow. Although there are clinical trials of myoblast delivery, the result is not satisfactory. However, human stem cell especially induced pluripotent stem cells （iPSCs） could overcome the problem by successful differentiation. Generally speaking, there are two strategies for that goal one is by plasmid and the other is by differentiation factors in vitro. This review covers recent advances in the differentiation field of human embryonic stem cells （ESCs） and iPSCs, showing different differentiation methods as a potential therapy way.展开更多
基金supported by the National Natural Science Foundation of China(3731530048C1202)
文摘With the development of high-throughput sequencing technology in the post-genomic era, researchers have concentrated their efforts on elucidating the relationships between genes and their corresponding functions. Recently, important progress has been achieved in the generation of genetically modified mice based on CRISPR/Cas9 and haploid embryonic stem cell （haESC） approaches, which provide new platforms for gene function analysis, human disease modeling, and gene therapy. Here, we review the CRISPR/Cas9 and haESC technology for the generation of genetically modified mice and discuss the key challenges in the application of these approaches.
基金supported by grants from the Ministry of Science and Technology of China(No.2009CB941101 to J.L.)the "Strategic Priority Research Program" of the Chinese Academy of Sciences(No.XDA01010403 to J.L.).
文摘Identification of the function of all genes in the mammalian genome is critical in understanding basic mechanisms of biology.However,the diploidy of mammalian somatic cells has greatly hindered efforts to elucidate the gene function in numerous biological processes by mutagenesis-based genetic approaches.Recently,mouse haploid embryonic stem(haES)cells have been successfully isolated from parthenogenetic and androgenetic embryos,providing an ideal tool for genetic analyses.In these studies,mouse haES cells have already shown that they could be used in cell-based forward or reverse genetic screenings and in generating gene-targeting via homologous recombination.In particular,haES cells from androgenetic embryos can be employed as novel,renewable form of fertilization agent for yielding live-born mice via injection into oocytes,thus showing the possibility that genetic analysis can be extended from cellular level to organism level.
基金National Key R&D Program of China (No.2018YFA0901101)the National Natural Science Foundation of China (Nos.22193050,92043301,22176203 and 22276212)the Sanming Project of Medicine in Shenzhen (No.SZSM201811070)。
文摘Investigating the development toxicity of perfuorinated iodine alkanes(PFIs)is critical,given their estrogenic effects through binding with estrogen receptors(ERs).In the present study,two PFIs,including dodecafuoro-1,6-diiodohexane(PFHx DI)and tridecafuorohexyl iodide(PFHx I),with binding preference to ERαand ERβ,respectively,were selected to evaluate their effects on proliferation and differentiation of the mouse embryonic stem cells(m ESCs).The results revealed that,similar to E_(2),50μmol/L PFHx DI accelerated the cell proliferation of the m ESCs.The PFI stimulation at the exposure concentrations of 2–50μmol/L promoted the differentiation of the m ESCs as characterized by the upregulation of differentiation-related biomarkers(i.e.,Otx2 and Dnmt3β)and downregulation of pluripotency genes(i.e.,Oct4,Nanog,Sox2,Prdm14 and Rex1).Comparatively,PFHx DI exhibited higher induction effect on the differentiation of the m ESCs than did PFHx I.The tests on ER signaling indicated that both PFI compounds induced exposure concentration-dependent expressions of ER signaling-related biomarkers(i.e.,ERα,ERβand Caveolin-1)in the m ESCs,and the downstream ER responsive genes(i.e.,c-fos,c-myc and c-jun)well responded to PFHx I stimulation.The role of ER in PFI-induced effects on the m ESCs was further validated by the antagonistic experiments using an ER inhibitor(ICI).The findings demonstrated that PFIs triggered ER signaling,and perturbed the differentiation program of the m ESCs,causing the potential health risk during early stage of development.
基金supported by a Chinese Academy of Sciences(CAS)Strategic Leading Science&Technology Program grant(XDB14040301)by the Hundred Talent Program of CAS(121311ZXPP2014004)at the Research Center for Eco-Environmental Sciences(RCEES),CAS
文摘The adverse effects of environmental pollution on our well-being have been intensively studied with many in vitro and in vivo systems. In our group, we focus on stem cell toxicology due to the multitude of embryonic stem cell（ESC） properties which can be exerted in toxicity assays. In fact, ESCs can differentiate in culture to mimic embryonic development in vivo, or specifically to virtually any kind of somatic cells. Here, we used the toxicant Bisphenol A（BPA）, a chemical known as a hazard to infants and children, and showed that our stem cell toxicology system was able to efficiently recapitulate most of the toxic effects of BPA previously detected by in vitro system or animal tests. More precisely, we demonstrated that BPA affected the proper specification of germ layers during our in vitro mimicking of the embryonic development, as well as the establishment of neural ectoderm and neural progenitor cells.
基金the Canada Research Chairs Program,the Canadian Institutes of Health Research,and the Natural Sciences and Engineering Research Council of Canada for their support
文摘There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is limited information available on their effects on neural development（Betts,2010;US EPA,2015）.
基金Supported by the State 863 High Technology R&D Project of China (Grant No. 2006AA02A107)the National Key Project for Basic Research of China (Grant No. 2005CB522702 to X. T. Pei)
文摘The self-renewal and pluripotency of embryonic stem cells (ESCs) is regulated by a network, which consists of a series of cell factors in microenviroments, a chain of transcription factors and certain signal conduction pathways. This article reviews recent progress in this field to elucidate the mecha-nism involved.
基金This work was supported by the Major State Basic Research Development Program of China(Grant No.2001CB509906)National 863 Hi-Tech Program(Grant Nos.2002AA205051&2003AA205160).
文摘Embryonic stem cells (ESCs), which are isolated from the inner cell mass of the blastocyst stage embryo, have the potential to give rise to an entire organism and to generate every body cell type. Much improvement has been made in the field of induction and differentia-tion of ESCs during the last two years, such as the ESCs differentiation into germ cells (2003) and the cloning of human ESCs (2004), both of which were chosen respectively as one of the top ten achievements evaluated by academic journals. Great attention was also paid to the research of the new genes which could maintain ESCs in the undifferentiated state and the research of the induction and differentiation of ESCs.
文摘Progress of cell therapy for muscular dystrophies is slow. Although there are clinical trials of myoblast delivery, the result is not satisfactory. However, human stem cell especially induced pluripotent stem cells （iPSCs） could overcome the problem by successful differentiation. Generally speaking, there are two strategies for that goal one is by plasmid and the other is by differentiation factors in vitro. This review covers recent advances in the differentiation field of human embryonic stem cells （ESCs） and iPSCs, showing different differentiation methods as a potential therapy way.
