Embryonic stem cells possess fascinating capacity of self-renewal and developmental potential,leading to significant progress in understanding the molecular basis of pluripotency,disease modeling,and reprogramming tec...Embryonic stem cells possess fascinating capacity of self-renewal and developmental potential,leading to significant progress in understanding the molecular basis of pluripotency,disease modeling,and reprogramming technology.Recently,2-cell-like embryonic stem cells(ESCs)and expanded potential stem cells or extended pluripotent stem cells(EPSCs)generated from early-cleavage embryos display some features of totipotent embryos.These cell lines provide valuable in vitro models to study underlying principles of totipotency,cell plasticity,and lineage segregation.In this review,we summarize the current progress in this filed and highlight the application potentials of these cells in the future.展开更多
Mouse embryonic stem cells(mESCs)cycle in and out of a transient 2-cell(2C)-like totipotent state,driven by a com-plex genetic circuit involves both the coding and repetitive sections of the genome.While a vast array ...Mouse embryonic stem cells(mESCs)cycle in and out of a transient 2-cell(2C)-like totipotent state,driven by a com-plex genetic circuit involves both the coding and repetitive sections of the genome.While a vast array of regulators,including the multi-functional protein Rif1,has been reported to influence the switch of fate potential,how they act in concert to achieve this cellular plasticity remains elusive.Here,by modularizing the known totipotency regulatory factors,we identify an unprecedented functional connection between Rif1 and the non-canonical polycomb repres-sive complex PRC1.6.Downregulation of the expression of either Rif1 or PRC1.6 subunits imposes similar impacts on the transcriptome of mESCs.The LacO-LacI induced ectopic colocalization assay detects a specific interaction between Rif1 and Pcgf6,bolstering the intactness of the PRC1.6 complex.Chromatin immunoprecipitation followed by sequencing(ChIP-seq)analysis further reveals that Rif1 is required for the accurate targeting of Pcgf6 to a group of genomic loci encompassing many genes involved in the regulation of the 2C-like state.Depletion of Rif1 or Pcgf6 not only activates 2C genes such as Zscan4 and Zfp352,but also derepresses a group of the endogenous retroviral element MERVL,a key marker for totipotency.Collectively,our findings discover that Rif1 can serve as a novel auxiliary component in the PRC1.6 complex to restrain the genetic circuit underlying totipotent fate potential,shedding new mechanistic insights into its function in regulating the cellular plasticity of embryonic stem cells.展开更多
2C型丝氨酸/苏氨酸蛋白磷酸酶(PP2C-type protein phosphatases, PP2C)是ABA信号转导途径中的关键组分,在植物生长发育、细胞周期调节及应对逆境胁迫的过程中发挥重要的作用。本研究利用本实验室构建的‘云烟87’转录组数据库,从‘云烟8...2C型丝氨酸/苏氨酸蛋白磷酸酶(PP2C-type protein phosphatases, PP2C)是ABA信号转导途径中的关键组分,在植物生长发育、细胞周期调节及应对逆境胁迫的过程中发挥重要的作用。本研究利用本实验室构建的‘云烟87’转录组数据库,从‘云烟87’烟草中克隆到一个NtPP2C37-like基因,该基因开放阅读框为1 275 bp,编码425个氨基酸残基。通过对NtPP2C37-like蛋白质进行相关分析,该蛋白不存在信号肽,可能属于非分泌蛋白;不具有跨膜结构,不属于跨膜蛋白。同源性分析结果显示,说明NtPP2C37-like蛋白与茄科植物有高度同源性。本研究获得了烟草NtPP2C37-like基因完整ORF,这为将来深入研究烟草NtPP2C37-like基因功能提供了科学依据。展开更多
基金supported by the National Natural Science Foundation of China(31970758)National Key R&D Program of China(2016YFA0102200,2017YFA0103301,2018YFC1004001)。
文摘Embryonic stem cells possess fascinating capacity of self-renewal and developmental potential,leading to significant progress in understanding the molecular basis of pluripotency,disease modeling,and reprogramming technology.Recently,2-cell-like embryonic stem cells(ESCs)and expanded potential stem cells or extended pluripotent stem cells(EPSCs)generated from early-cleavage embryos display some features of totipotent embryos.These cell lines provide valuable in vitro models to study underlying principles of totipotency,cell plasticity,and lineage segregation.In this review,we summarize the current progress in this filed and highlight the application potentials of these cells in the future.
基金This project has been supported by the National Natural Science Foundation of China(32170821,31771589 to K.Y)Ministry of Science and Technology of the People’s Republic of China(2021YFC2701202)+1 种基金Department of Science&Technology of Hunan Province(2021JJ10054,2019SK1012,2018DK2015,2017RS3013,2017XK2011 to K.Y,2019JJ40478 to P.L,and the innovative team program 2019RS1010)Central South University(2018CX032 to K.Y,and the innovation-driven team project 2020CX016)。
文摘Mouse embryonic stem cells(mESCs)cycle in and out of a transient 2-cell(2C)-like totipotent state,driven by a com-plex genetic circuit involves both the coding and repetitive sections of the genome.While a vast array of regulators,including the multi-functional protein Rif1,has been reported to influence the switch of fate potential,how they act in concert to achieve this cellular plasticity remains elusive.Here,by modularizing the known totipotency regulatory factors,we identify an unprecedented functional connection between Rif1 and the non-canonical polycomb repres-sive complex PRC1.6.Downregulation of the expression of either Rif1 or PRC1.6 subunits imposes similar impacts on the transcriptome of mESCs.The LacO-LacI induced ectopic colocalization assay detects a specific interaction between Rif1 and Pcgf6,bolstering the intactness of the PRC1.6 complex.Chromatin immunoprecipitation followed by sequencing(ChIP-seq)analysis further reveals that Rif1 is required for the accurate targeting of Pcgf6 to a group of genomic loci encompassing many genes involved in the regulation of the 2C-like state.Depletion of Rif1 or Pcgf6 not only activates 2C genes such as Zscan4 and Zfp352,but also derepresses a group of the endogenous retroviral element MERVL,a key marker for totipotency.Collectively,our findings discover that Rif1 can serve as a novel auxiliary component in the PRC1.6 complex to restrain the genetic circuit underlying totipotent fate potential,shedding new mechanistic insights into its function in regulating the cellular plasticity of embryonic stem cells.
