In Vivo Differentiation Potential of Epiblast Stem Cells Revealed by Chimeric Embryo Formation

In Vivo Differentiation Potential of Epiblast Stem Cells Revealed by Chimeric Embryo Formation
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DOI:
10.1016/j.celrep.2012.10.022
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发表时间:
2012-12-01
期刊:
影响因子:
8.8
通讯作者:
Wilson, Valerie
Wilson, Valerie
中科院分区:
生物学1区
文献类型:
--
作者:
Huang, Yali;Osorno, Rodrigo;Wilson, Valerie

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囊胚注射或桑葚胚聚集后嵌合体的形成是小鼠胚胎干细胞(ESCs)发育潜力的主要功能测定。这一特性证明了ESCs和着床前外胚层之间的功能等同,但外胚层干细胞(EpiSC)系并不具有这一特性。本研究表明,体外培养的EpiSCs无论是来自体外培养的胚胎,还是来自体外培养的ESCs,当移植到体外培养的胚胎上时,都很容易产生嵌合体。EpiSC衍生物整合并分化为所有三种胚胎胚层和原始生殖细胞的衍生物。相比之下,移植的ESCs很少在移植后胚胎中增殖,并且无法获得其宿主来源的邻居的身份。EpiSCs不能有效地结合到胚胎期8.5天的胚胎中,在这个阶段多能性已经丧失。因此,EpiSCs嵌合体的形成需要一个允许的环境,即植入后的外胚层,并证明了这种细胞类型与EpiSCs之间的功能等效。
Chimera formation after blastocyst injection or morula aggregation is the principal functional assay of the developmental potential of mouse embryonic stem cells (ESCs). This property, which demonstrates functional equivalence between ESCs and the preimplantation epiblast, is not shared by epiblast stem cell (EpiSC) lines. Here, we show that EpiSCs derived either from postimplantation embryos or from ESCs in vitro readily generate chimeras when grafted to postimplantation embryos in whole embryo culture. EpiSC derivatives integrate and differentiate to derivatives of all three embryonic germ layers and primordial germ cells. In contrast, grafted ESCs seldom proliferate in postimplantation embryos, and fail to acquire the identity of their host-derived neighbors. EpiSCs do not incorporate efficiently into embryonic day 8.5 embryos, a stage by which pluripotency has been lost. Thus, chimera formation by EpiSCs requires a permissive environment, the postimplantation epiblast, and demonstrates functional equivalence between this cell type and EpiSCs.