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
Transposable elements,long considered genomic intruders,have been found to play significant and intriguing roles during early embryonic development based on the paradigm shift that has undergone in recent years.Long i...Transposable elements,long considered genomic intruders,have been found to play significant and intriguing roles during early embryonic development based on the paradigm shift that has undergone in recent years.Long interspersed element-1(LINE-1)is the predominant class of retrotransposons with autonomous retrotransposition capabilities in mammals and has emerged as a crucial element of preimplantation development.In this review,we elucidate the expression dynamics of key transposable elements throughout preimplantation development and their contribution to the regulation of developmental progression and totipotency.We also explore the critical function of LINE-1 activation and its rich functional reservoir,which is exploited by the host to provide cis-regulatory elements and functional proteins.Particular highlights of the widespread activities in preimplantation development of LINE-1 during multiple epigenetic modifications such as DNA methylation,histone methylation,ubiquitination,and RNA methylation.The silencing complex and RNA exosome also coordinate with LINE-1 across distinct developmental stages.Accordingly,the up-regulated expression of LINE-1 retrotransposons and their protein products plays a key role in various processes,including the opening of chromatin architecture,zygotic genome activation,aging,and age-related disorders.It may reflect an effect on totipotency and pluripotency of mammalian development.Underscoring its pivotal significance,the nuanced regulation of LINE-1 illuminates its indispensable role in orchestrating the precise coordination essential for the regulation of cellular pluripotency and the intricate mechanisms of zygotic genome activation.展开更多
Plant cells have a powerful capacity in their propagation to adapt to environmental change, given that a single plant cell can give rise to a whole plant via somatic embryogenesis without the need for fertilization. T...Plant cells have a powerful capacity in their propagation to adapt to environmental change, given that a single plant cell can give rise to a whole plant via somatic embryogenesis without the need for fertilization. The reprogramming of somatic cells into totipotent cells is a critical step in somatic embryogenesis. This process can be induced by stimuli such as plant hormones, transcriptional regulators and stress. Here, we review current knowledge on how the identity of totipotent cells is determined and the stimuli required for reprogramming of somatic cells into totipotent cells. We highlight key molecular regulators and associated networks that control cell fate transition from somatic to totipotent cells. Finally,we pose several outstanding questions that should be addressed to enhance our understanding of the mechanisms underlying plant cell totipotency.展开更多
Pluripotent stem cells(PSCs)are useful for developmental and translational research because they have the potential to differentiate into all cell types of an adult individual.Pigs are one of the most important domest...Pluripotent stem cells(PSCs)are useful for developmental and translational research because they have the potential to differentiate into all cell types of an adult individual.Pigs are one of the most important domestic ungulates,commonly used for food and as bioreactors.Generating stable pluripotent porcine PSC lines remains challenging.So far,the pluripotency gene network of porcine PSCs is poorly understood.Here we found that TBX3-derived induced pluripotent stem cells(iPSCs)closely resemble porcine 4-cell embryos with the capacity of totipotent-like stem cells(TLSCs).Interestingly,our data suggest that TBX3 facilitates the activation of H3K4me3 methyltransferase,specifically MLL1.Subsequent investigations revealed that the porcine 4-cell specific gene,MCL1,is a key downstream effector of the TBX3-MLL1 axis.Together,our study of the TBX3 regulatory network is helpful in the understanding of the totipotency characteristics of pigs.展开更多
Mammalian cell totipotency is a subject that has fascinated scientists for generations. A long lasting question whether some of the somatic cells retains totipotency was answered by the cloning of Dolly at the end of ...Mammalian cell totipotency is a subject that has fascinated scientists for generations. A long lasting question whether some of the somatic cells retains totipotency was answered by the cloning of Dolly at the end of the 20th century. The dawn of the 21st has brought forward great expectations in harnessing the power of totipotentcy in medicine. Through stem cell biology, it is possible to generate any parts of the human body by stem cell engineering. Considerable resources will be devoted to harness the untapped potentials of stem cells in the foreseeable future which may transform medicine as we know today. At the molecular level, totipotency has been linked to a singular transcription factor and its expression appears to define whether a cell should be totipotent. Named Oct4, it can activate or repress the expression of various genes. Curiously, very little is known about Oct4 beyond its ability to regulate gene expression. The mechanism by which Oct4 specifies totipotency remains entirely unresolved. In this review, we summarize the structure and function of Oct4 and address issues related to Oct4 function in maintaining totipotency or pluripotency of embryonic stem cells.展开更多
Peach palm(Bactris gasipaes Kunth)has been micropropagated from pre-procambial cells that provide stem-like cell niches,(i.e.,pre-procambial cells),multipotent,pluripotent and totipotent for direct vascularization,adv...Peach palm(Bactris gasipaes Kunth)has been micropropagated from pre-procambial cells that provide stem-like cell niches,(i.e.,pre-procambial cells),multipotent,pluripotent and totipotent for direct vascularization,adventitious buds and somatic embryogenesis,respectively.The direct induction of adventitious buds and somatic embryogenesis reduces the frequency of mutations when compared to indirect morphogenesis.Long-term in vitro cultivation of perennial species such as peach palm cause the clones to age and deteriorate;however,the consequences for morphogenesis potential are not fully clear.The morphogenic potential of peach palm clones established and in vitro cultivated for 8 years(regeneration of adventitious buds without callus formation)was investigated in leaves,roots and stem bases using histological and histochemical analyses.Data from long-term cultures(8-years-old)was compared to data from short-term cultures(1-year-old).Morphogenic pathways monitoring for direct induction of somatic embryos and adventitious buds revealed a strong morphogenic reduction potential in the pre-procambial cells,parenchyma cells in the proximal region of stem bases,and external cells of leaf sheaths.Initial cells of shoot apical meristems and pre-procambial cells commit cell reprogramming to the undifferentiated state and subsequent acquisition of cellular competence.These results are applicable in the micropropagation of peach palm,with consideration to obtaining clones and their long-term in vitro culture.展开更多
As an alternative model for studying the dynamic process of early mammalian embryonic development,much progress has been made in using mouse embryonic stem cells(mESCs)to generate embryo-like structures,especially by ...As an alternative model for studying the dynamic process of early mammalian embryonic development,much progress has been made in using mouse embryonic stem cells(mESCs)to generate embryo-like structures,especially by modifying the starting cells.A previous study has demonstrated that totipotent blastomere-like cells(TBLCs)can be obtained by continuous treatment of mESCs with a low-dose splicing inhibitor,Pladienolide B(PlaB).However,these totipotent mESCs have limited proliferative capacity.Here,we report that short-term highdose PlaB treatment can also induce mESCs to acquire totipotency.This treatment equips this novel type of stem cells with the ability to selforganize into blastoids and recapitulate key preimplantation developmental processes.Therefore,the stem cells are termed transient totipotent blastomere-like stem cells(tTBLCs).Transcriptome analysis showed that tTBLC blastoids bore similarities to mouse E3.5 blastocysts,E4.5 blastocysts,and TBLC blastoids.Additionally,we found that tTBLC blastoids could develop beyond the implantation stage,forming egg-cylinder-like structures both in vitro and in vivo.In summary,our research provides an alternative rapid and convenient method to generate the starting cells capable of developing into blastoids,which have immense application in various fields,not only in the basic study of early mouse embryogenesis but also in high-throughput drug screening.展开更多
The giant panda skeletal muscle cells, uterus epithelial cells and mammary gland cells from an adult individual were cultured and used as nucleus donor for the construction of interspecies embryos by transferring them...The giant panda skeletal muscle cells, uterus epithelial cells and mammary gland cells from an adult individual were cultured and used as nucleus donor for the construction of interspecies embryos by transferring them into enucleated rabbit eggs. All the three kinds of somatic cells were able to reprogram in rabbit ooplasm and support early embryo development, of which mammary gland cells were proven to be the best, followed by uterus epithelial cells and skeletal muscle cells. The experiments showed that direct injection of mammary gland cell into enucleated rabbit ooplasm, combined with in vivo development in ligated rabbit oviduct, achieved higher blastocyst development than in vitro culture after the somatic cell was injected into the perivitelline space and fused with the enucleated egg by electrical stimulation. The chromosome analysis demonstrated that the genetic materials in reconstructed blastocyst cells were the same as that in panda somatic cells. In addition, giant panda mitochondrial DNA (mtDNA) was shown to exist in the interspecies reconstructed blastocyst. The data suggest that (i) the ability of ooplasm to dedifferentiate somatic cells is not species-specific; (ii) there is compatibility between interspecies somatic nucleus and ooplasm during early development of the reconstructed egg.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
Oct4 is a key component of the pluripotency regulatory network,and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells(ESCs)or their differentiati...Oct4 is a key component of the pluripotency regulatory network,and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells(ESCs)or their differentiation into trophoblast.Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development.However,the genetic elimination of maternal Oct4 using a Cre-lox approach in mouse revealed that the establishment of totipotency in maternal Oct4–depleted embryos was not affected,and that these embryos could complete full-term development without any obvious defect.These results indicate that Oct4 is not essential for the initiation of pluripotency,in contrast to its critical role in maintaining pluripotency.This conclusion is further supported by the formation of Oct4-GFP–and Nanog-expressing inner cell masses(ICMs)in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.展开更多
Mammalian embryogenesis begins with a totipotent zygote.Blastocyst-like structures can be captured by aggregated cells with extended pluripotent properties in a three-dimensional(3D)culture system.However,the efficien...Mammalian embryogenesis begins with a totipotent zygote.Blastocyst-like structures can be captured by aggregated cells with extended pluripotent properties in a three-dimensional(3D)culture system.However,the efficiency of generating blastoids is low,and it remains unclear whether other reported totipotent-like stem cells retain a similar capacity.In this study,we demonstrated that spliceosomal repression-induced totipotent blastomere-like cells(TBLCs)form blastocyst-like structures within around 80%of all microwells.In addition,we generated blastoids initiating from a single TBLC.TBLC-blastoids express specific markers of constituent cell lineages of a blastocyst and resemble blastocyst in cell-lineage allocation.Moreover,singlecell RNA sequencing revealed that TBLC-blastoids share a similar transcriptional profile to natural embryos,albeit composed of fewer primitive endoderm-like cells.Furthermore,TBLC-blastoids can develop beyond the implantation stage in vitro and induce decidualization in vivo.In summary,our findings provided an alternative cell type to efficiently generate blastoids for the study of early mouse embryogenesis.展开更多
Subject Code:C07 With the support of the National Natural Science Foundation of China,a research group led by Prof.Deng Hongkui(邓宏魁)from Peking University,in collaboration with researchers from the Salk Institute a...Subject Code:C07 With the support of the National Natural Science Foundation of China,a research group led by Prof.Deng Hongkui(邓宏魁)from Peking University,in collaboration with researchers from the Salk Institute and Peking University People’s Hospital,demonstrates that the developmental potentials of stem cell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supported by grants from the National Natural Science Foundation of China(No.32371217,32070860)the National Key R&D Plan of China(No.2021YFA1101002)+1 种基金Tianjin Natural Science Foundation(China)(No.22JCYBJC01220)the National Students'Platform for Innovation and Entrepreneurship Training Program(China)(No.202410055320,202410055676).
文摘Transposable elements,long considered genomic intruders,have been found to play significant and intriguing roles during early embryonic development based on the paradigm shift that has undergone in recent years.Long interspersed element-1(LINE-1)is the predominant class of retrotransposons with autonomous retrotransposition capabilities in mammals and has emerged as a crucial element of preimplantation development.In this review,we elucidate the expression dynamics of key transposable elements throughout preimplantation development and their contribution to the regulation of developmental progression and totipotency.We also explore the critical function of LINE-1 activation and its rich functional reservoir,which is exploited by the host to provide cis-regulatory elements and functional proteins.Particular highlights of the widespread activities in preimplantation development of LINE-1 during multiple epigenetic modifications such as DNA methylation,histone methylation,ubiquitination,and RNA methylation.The silencing complex and RNA exosome also coordinate with LINE-1 across distinct developmental stages.Accordingly,the up-regulated expression of LINE-1 retrotransposons and their protein products plays a key role in various processes,including the opening of chromatin architecture,zygotic genome activation,aging,and age-related disorders.It may reflect an effect on totipotency and pluripotency of mammalian development.Underscoring its pivotal significance,the nuanced regulation of LINE-1 illuminates its indispensable role in orchestrating the precise coordination essential for the regulation of cellular pluripotency and the intricate mechanisms of zygotic genome activation.
基金funded by the National Natural Science Foundation of China (31730008, 31872669)the Major Program of Shandong Provincial Natural Science Foundation(2017C03)。
文摘Plant cells have a powerful capacity in their propagation to adapt to environmental change, given that a single plant cell can give rise to a whole plant via somatic embryogenesis without the need for fertilization. The reprogramming of somatic cells into totipotent cells is a critical step in somatic embryogenesis. This process can be induced by stimuli such as plant hormones, transcriptional regulators and stress. Here, we review current knowledge on how the identity of totipotent cells is determined and the stimuli required for reprogramming of somatic cells into totipotent cells. We highlight key molecular regulators and associated networks that control cell fate transition from somatic to totipotent cells. Finally,we pose several outstanding questions that should be addressed to enhance our understanding of the mechanisms underlying plant cell totipotency.
基金funded by the National Basic Research Program of China(2022YFD1302200,2023YFF1000904,2023ZD0404303 and 2021YFD1200301)the National Natural Science Foundation of China(32072806,32372970 and 32002246)+2 种基金the Program of Shaanxi Province Science and Technology Innovation Team,China(2019TD-036)the Key Technologies Demonstration of Animal Husbandry in Shaanxi Province,China(20221086 and 20230978)the Inner Mongolia Autonomous Region Open Competition Project,China(2022JBGS0025).
文摘Pluripotent stem cells(PSCs)are useful for developmental and translational research because they have the potential to differentiate into all cell types of an adult individual.Pigs are one of the most important domestic ungulates,commonly used for food and as bioreactors.Generating stable pluripotent porcine PSC lines remains challenging.So far,the pluripotency gene network of porcine PSCs is poorly understood.Here we found that TBX3-derived induced pluripotent stem cells(iPSCs)closely resemble porcine 4-cell embryos with the capacity of totipotent-like stem cells(TLSCs).Interestingly,our data suggest that TBX3 facilitates the activation of H3K4me3 methyltransferase,specifically MLL1.Subsequent investigations revealed that the porcine 4-cell specific gene,MCL1,is a key downstream effector of the TBX3-MLL1 axis.Together,our study of the TBX3 regulatory network is helpful in the understanding of the totipotency characteristics of pigs.
文摘Mammalian cell totipotency is a subject that has fascinated scientists for generations. A long lasting question whether some of the somatic cells retains totipotency was answered by the cloning of Dolly at the end of the 20th century. The dawn of the 21st has brought forward great expectations in harnessing the power of totipotentcy in medicine. Through stem cell biology, it is possible to generate any parts of the human body by stem cell engineering. Considerable resources will be devoted to harness the untapped potentials of stem cells in the foreseeable future which may transform medicine as we know today. At the molecular level, totipotency has been linked to a singular transcription factor and its expression appears to define whether a cell should be totipotent. Named Oct4, it can activate or repress the expression of various genes. Curiously, very little is known about Oct4 beyond its ability to regulate gene expression. The mechanism by which Oct4 specifies totipotency remains entirely unresolved. In this review, we summarize the structure and function of Oct4 and address issues related to Oct4 function in maintaining totipotency or pluripotency of embryonic stem cells.
文摘Peach palm(Bactris gasipaes Kunth)has been micropropagated from pre-procambial cells that provide stem-like cell niches,(i.e.,pre-procambial cells),multipotent,pluripotent and totipotent for direct vascularization,adventitious buds and somatic embryogenesis,respectively.The direct induction of adventitious buds and somatic embryogenesis reduces the frequency of mutations when compared to indirect morphogenesis.Long-term in vitro cultivation of perennial species such as peach palm cause the clones to age and deteriorate;however,the consequences for morphogenesis potential are not fully clear.The morphogenic potential of peach palm clones established and in vitro cultivated for 8 years(regeneration of adventitious buds without callus formation)was investigated in leaves,roots and stem bases using histological and histochemical analyses.Data from long-term cultures(8-years-old)was compared to data from short-term cultures(1-year-old).Morphogenic pathways monitoring for direct induction of somatic embryos and adventitious buds revealed a strong morphogenic reduction potential in the pre-procambial cells,parenchyma cells in the proximal region of stem bases,and external cells of leaf sheaths.Initial cells of shoot apical meristems and pre-procambial cells commit cell reprogramming to the undifferentiated state and subsequent acquisition of cellular competence.These results are applicable in the micropropagation of peach palm,with consideration to obtaining clones and their long-term in vitro culture.
基金supported by the National Natural Science Foundation of China(32070804,82271690,32170742)the National Key Research and Development Program of China(2022YFC2702500)the Start Fund for High-level Talents of Nanjing Medical University(NMUR2020009).
文摘As an alternative model for studying the dynamic process of early mammalian embryonic development,much progress has been made in using mouse embryonic stem cells(mESCs)to generate embryo-like structures,especially by modifying the starting cells.A previous study has demonstrated that totipotent blastomere-like cells(TBLCs)can be obtained by continuous treatment of mESCs with a low-dose splicing inhibitor,Pladienolide B(PlaB).However,these totipotent mESCs have limited proliferative capacity.Here,we report that short-term highdose PlaB treatment can also induce mESCs to acquire totipotency.This treatment equips this novel type of stem cells with the ability to selforganize into blastoids and recapitulate key preimplantation developmental processes.Therefore,the stem cells are termed transient totipotent blastomere-like stem cells(tTBLCs).Transcriptome analysis showed that tTBLC blastoids bore similarities to mouse E3.5 blastocysts,E4.5 blastocysts,and TBLC blastoids.Additionally,we found that tTBLC blastoids could develop beyond the implantation stage,forming egg-cylinder-like structures both in vitro and in vivo.In summary,our research provides an alternative rapid and convenient method to generate the starting cells capable of developing into blastoids,which have immense application in various fields,not only in the basic study of early mouse embryogenesis but also in high-throughput drug screening.
基金Project supported by the 1998 Special Fund of the Chinese Academy of Sciences (KY95-J1-318)a 1999 Special Fund from the Ministry of ScienceTechnology.Instruments were dominated by Mr. Shum Yam Wa, Heal Force Development Ltd
文摘The giant panda skeletal muscle cells, uterus epithelial cells and mammary gland cells from an adult individual were cultured and used as nucleus donor for the construction of interspecies embryos by transferring them into enucleated rabbit eggs. All the three kinds of somatic cells were able to reprogram in rabbit ooplasm and support early embryo development, of which mammary gland cells were proven to be the best, followed by uterus epithelial cells and skeletal muscle cells. The experiments showed that direct injection of mammary gland cell into enucleated rabbit ooplasm, combined with in vivo development in ligated rabbit oviduct, achieved higher blastocyst development than in vitro culture after the somatic cell was injected into the perivitelline space and fused with the enucleated egg by electrical stimulation. The chromosome analysis demonstrated that the genetic materials in reconstructed blastocyst cells were the same as that in panda somatic cells. In addition, giant panda mitochondrial DNA (mtDNA) was shown to exist in the interspecies reconstructed blastocyst. The data suggest that (i) the ability of ooplasm to dedifferentiate somatic cells is not species-specific; (ii) there is compatibility between interspecies somatic nucleus and ooplasm during early development of the reconstructed egg.
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.
基金This research was supported by the Max Planck Society,DFG grant SI 1695/1-2(SPP1356)NIH grant R01HD059946-01 from the Eunice Kennedy Shriver National Institute of Child Health&Human Development.We thank Areti Malapetsas for final editing。
文摘Oct4 is a key component of the pluripotency regulatory network,and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells(ESCs)or their differentiation into trophoblast.Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development.However,the genetic elimination of maternal Oct4 using a Cre-lox approach in mouse revealed that the establishment of totipotency in maternal Oct4–depleted embryos was not affected,and that these embryos could complete full-term development without any obvious defect.These results indicate that Oct4 is not essential for the initiation of pluripotency,in contrast to its critical role in maintaining pluripotency.This conclusion is further supported by the formation of Oct4-GFP–and Nanog-expressing inner cell masses(ICMs)in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.
基金supported by the National Natural Science Foundation of China(32070800)。
文摘Mammalian embryogenesis begins with a totipotent zygote.Blastocyst-like structures can be captured by aggregated cells with extended pluripotent properties in a three-dimensional(3D)culture system.However,the efficiency of generating blastoids is low,and it remains unclear whether other reported totipotent-like stem cells retain a similar capacity.In this study,we demonstrated that spliceosomal repression-induced totipotent blastomere-like cells(TBLCs)form blastocyst-like structures within around 80%of all microwells.In addition,we generated blastoids initiating from a single TBLC.TBLC-blastoids express specific markers of constituent cell lineages of a blastocyst and resemble blastocyst in cell-lineage allocation.Moreover,singlecell RNA sequencing revealed that TBLC-blastoids share a similar transcriptional profile to natural embryos,albeit composed of fewer primitive endoderm-like cells.Furthermore,TBLC-blastoids can develop beyond the implantation stage in vitro and induce decidualization in vivo.In summary,our findings provided an alternative cell type to efficiently generate blastoids for the study of early mouse embryogenesis.
文摘Subject Code:C07 With the support of the National Natural Science Foundation of China,a research group led by Prof.Deng Hongkui(邓宏魁)from Peking University,in collaboration with researchers from the Salk Institute and Peking University People’s Hospital,demonstrates that the developmental potentials of stem cell
