小鼠扩展潜能干细胞的建立。
Establishment of mouse expanded potential stem cells.
作者信息
Yang Jian, Ryan David J, Wang Wei, Tsang Jason Cheuk-Ho, Lan Guocheng, Masaki Hideki, Gao Xuefei, Antunes Liliana, Yu Yong, Zhu Zhexin, Wang Juexuan, Kolodziejczyk Aleksandra A, Campos Lia S, Wang Cui, Yang Fengtang, Zhong Zhen, Fu Beiyuan, Eckersley-Maslin Melanie A, Woods Michael, Tanaka Yosuke, Chen Xi, Wilkinson Adam C, Bussell James, White Jacqui, Ramirez-Solis Ramiro, Reik Wolf, Göttgens Berthold, Teichmann Sarah A, Tam Patrick P L, Nakauchi Hiromitsu, Zou Xiangang, Lu Liming, Liu Pentao
机构信息
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK.
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
出版信息
Nature. 2017 Oct 19;550(7676):393-397. doi: 10.1038/nature24052. Epub 2017 Oct 11.
Mouse embryonic stem cells derived from the epiblast contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species.
源自上胚层的小鼠胚胎干细胞可分化为体细胞谱系和生殖系，但在重新植入囊胚后，它们会被排除在源自滋养外胚层和原始内胚层的胚外组织之外。在此，我们报告了可从单个八细胞卵裂球中建立扩展潜能干细胞培养物，并通过直接转化小鼠胚胎干细胞和诱导多能干细胞来实现。值得注意的是，在嵌合体实验中，单个扩展潜能干细胞既能对胚胎本身做出贡献，也能对滋养外胚层谱系做出贡献。真正的滋养层干细胞系和胚外内胚层干细胞可在体外直接从扩展潜能干细胞中获得。对表观基因组和单细胞转录组的分子分析揭示了扩展潜能干细胞中卵裂球特异性特征的富集以及动态的DNA甲基化组。小鼠扩展潜能干细胞的产生突出了为其他哺乳动物物种建立扩展潜能干细胞的可行性。
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