Haploid pluripotent stem cells,such as haploid embryonic stem cells(haESCs),facilitate the genetic study of recessive traits.In vitro,fish haESCs maintain haploidy in both undifferentiated and differentiated states,bu...Haploid pluripotent stem cells,such as haploid embryonic stem cells(haESCs),facilitate the genetic study of recessive traits.In vitro,fish haESCs maintain haploidy in both undifferentiated and differentiated states,but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested.Here,wereport thatmousehaESCs can differentiate in vitro into haploid epiblast stem cells(haEpiSCs),which maintain an intact haploid genome,unlimited self-renewal potential,and durable pluripotency to differentiate into various tissues in vitro and in vivo.Mechanistically,the maintenance of self-renewal potential depends on the Activin/bFGF pathway.We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.When injected into the cytoplasm of an oocyte,androgenetic haEpiSC(ahaEpiSCs)can support embryonic development until midgestation(E12.5).Together,these resultsdemonstrate durable pluripotency inmousehaESCs andhaEpiSCs,aswell asthe valuable potential of using these haploid pluripotent stem cells in high-throughput genetic screening.展开更多
Normal mouse pluripotent stem cells were originally derived from the inner cell mass(ICM) of blastocysts and shown to be the in vitro equivalent of those pre-implantation embryonic cells, and thus were called embryoni...Normal mouse pluripotent stem cells were originally derived from the inner cell mass(ICM) of blastocysts and shown to be the in vitro equivalent of those pre-implantation embryonic cells, and thus were called embryonic stem cells(ESCs). More than a decade later, pluripotent cells were isolated from the ICM of human blastocysts. Despite being called human ESCs, these cells differ significantly from mouse ESCs, including different morphology and mechanisms of control of pluripotency, suggesting distinct embryonic origins of ESCs from the two species. Subsequently, mouse pluripotent stem cells were established from the ICMderived epiblast of post-implantation embryos. These mouse epiblast stem cells(Epi SCs) are morphological and epigenetically more similar to human ESCs. This raised the question of whether cells from the human ICM are in a more advanced differentiation stage than their murine counterpart, or whether the available culture conditions were not adequate to maintain those human cells in their in vivo state, leading to a transition into Epi SC-like cells in vitro. More recently, novel culture conditions allowed the conversion of human ESCs into mouse ESC-like cells called nave(or ground state) human ESCs, and the derivation of nave human ESCs from blastocysts. Here we will review the characteristics of each type of pluripotent stem cells, how(and whether) these relate to different stages of embryonic development, and discuss the potential implications of nave human ESCs in research and therapy.展开更多
Pluripotency is depicted by a self-renewing state that can competently differentiate to form the three germ layers.Different stages of early murine development can be captured on a petri dish,delineating a spectrum of...Pluripotency is depicted by a self-renewing state that can competently differentiate to form the three germ layers.Different stages of early murine development can be captured on a petri dish,delineating a spectrum of pluripotent states,ranging from embryonic stem cells,embryonic germ cells to epiblast stem cells.Anomalous cell populations displaying signs of pluripotency have also been uncovered,from the isolation of embryonic carcinoma cells to the derivation of induced pluripotent stem cells.Gaining insight into the molecular circuitry within these cell types enlightens us about the significance and contribution of each stage,hence deepening our understanding of vertebrate development.In this review,we aim to describe experimental milestones that led to the understanding of embryonic development and the conception of pluripotency.We also discuss attempts at exploring the realm of pluripotency with the identification of pluripotent stem cells within mouse teratocarcinomas and embryos,and the generation of pluripotent cells through nuclear reprogramming.In conclusion,we illustrate pluripotent cells derived from other organisms,including human derivatives,and describe current paradigms in the comprehension of human pluripotency.展开更多
基金supported by grants from the National Basic Research Program of China(2012CBA01300 to Q.Z.and 2014CB964800 to W.L.)the National Science Foundation of China(91319308 to Q.Z.).
文摘Haploid pluripotent stem cells,such as haploid embryonic stem cells(haESCs),facilitate the genetic study of recessive traits.In vitro,fish haESCs maintain haploidy in both undifferentiated and differentiated states,but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested.Here,wereport thatmousehaESCs can differentiate in vitro into haploid epiblast stem cells(haEpiSCs),which maintain an intact haploid genome,unlimited self-renewal potential,and durable pluripotency to differentiate into various tissues in vitro and in vivo.Mechanistically,the maintenance of self-renewal potential depends on the Activin/bFGF pathway.We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.When injected into the cytoplasm of an oocyte,androgenetic haEpiSC(ahaEpiSCs)can support embryonic development until midgestation(E12.5).Together,these resultsdemonstrate durable pluripotency inmousehaESCs andhaEpiSCs,aswell asthe valuable potential of using these haploid pluripotent stem cells in high-throughput genetic screening.
基金Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Departamento de Ciencia e Tecnologia do Ministerio da Saude(CNPq/MS/DECIT)Banco Nacional de Desenvolvimento Economico e Social(BNDES)+2 种基金Financiadora de Estudos e Projetos(FINEP)the fellowship from CNPq(Costas RM)a fellowship from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior(Fonseca SAS)
文摘Normal mouse pluripotent stem cells were originally derived from the inner cell mass(ICM) of blastocysts and shown to be the in vitro equivalent of those pre-implantation embryonic cells, and thus were called embryonic stem cells(ESCs). More than a decade later, pluripotent cells were isolated from the ICM of human blastocysts. Despite being called human ESCs, these cells differ significantly from mouse ESCs, including different morphology and mechanisms of control of pluripotency, suggesting distinct embryonic origins of ESCs from the two species. Subsequently, mouse pluripotent stem cells were established from the ICMderived epiblast of post-implantation embryos. These mouse epiblast stem cells(Epi SCs) are morphological and epigenetically more similar to human ESCs. This raised the question of whether cells from the human ICM are in a more advanced differentiation stage than their murine counterpart, or whether the available culture conditions were not adequate to maintain those human cells in their in vivo state, leading to a transition into Epi SC-like cells in vitro. More recently, novel culture conditions allowed the conversion of human ESCs into mouse ESC-like cells called nave(or ground state) human ESCs, and the derivation of nave human ESCs from blastocysts. Here we will review the characteristics of each type of pluripotent stem cells, how(and whether) these relate to different stages of embryonic development, and discuss the potential implications of nave human ESCs in research and therapy.
文摘Pluripotency is depicted by a self-renewing state that can competently differentiate to form the three germ layers.Different stages of early murine development can be captured on a petri dish,delineating a spectrum of pluripotent states,ranging from embryonic stem cells,embryonic germ cells to epiblast stem cells.Anomalous cell populations displaying signs of pluripotency have also been uncovered,from the isolation of embryonic carcinoma cells to the derivation of induced pluripotent stem cells.Gaining insight into the molecular circuitry within these cell types enlightens us about the significance and contribution of each stage,hence deepening our understanding of vertebrate development.In this review,we aim to describe experimental milestones that led to the understanding of embryonic development and the conception of pluripotency.We also discuss attempts at exploring the realm of pluripotency with the identification of pluripotent stem cells within mouse teratocarcinomas and embryos,and the generation of pluripotent cells through nuclear reprogramming.In conclusion,we illustrate pluripotent cells derived from other organisms,including human derivatives,and describe current paradigms in the comprehension of human pluripotency.
