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形成多能干细胞表现出胚外细胞的特征，这些胚外细胞为原肠胚形成做好了准备。

Formative pluripotent stem cells show features of epiblast cells poised for gastrulation.

机构信息

State Key Laboratory of Stem Cell and Reproductive Biology, Innovation Academy for Stem Cell and Regeneration, Beijing Institute for Stem Cell and Regenerative Medicine, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100101, China.

Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China.

出版信息

Cell Res. 2021 May;31(5):526-541. doi: 10.1038/s41422-021-00477-x. Epub 2021 Feb 19.

DOI:10.1038/s41422-021-00477-x
PMID:33608671
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8089102/
Abstract

The pluripotency of mammalian early and late epiblast could be recapitulated by naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), respectively. However, these two states of pluripotency may not be sufficient to reflect the full complexity and developmental potency of the epiblast during mammalian early development. Here we report the establishment of self-renewing formative pluripotent stem cells (fPSCs) which manifest features of epiblast cells poised for gastrulation. fPSCs can be established from different mouse ESCs, pre-/early-gastrula epiblasts and induced PSCs. Similar to pre-/early-gastrula epiblasts, fPSCs show the transcriptomic features of formative pluripotency, which are distinct from naïve ESCs and primed EpiSCs. fPSCs show the unique epigenetic states of E6.5 epiblast, including the super-bivalency of a large set of developmental genes. Just like epiblast cells immediately before gastrulation, fPSCs can efficiently differentiate into three germ layers and primordial germ cells (PGCs) in vitro. Thus, fPSCs highlight the feasibility of using PSCs to explore the development of mammalian epiblast.

摘要

哺乳动物早期和晚期上胚层的多能性分别可以通过原始胚胎干细胞 (ESCs) 和初始上胚层干细胞 (EpiSCs) 来重编程。然而，这两种多能性状态可能不足以反映哺乳动物早期发育中上胚层的全部复杂性和发育潜能。在这里，我们报告了自我更新的形成多能性干细胞 (fPSCs) 的建立，这些细胞表现出处于原肠胚形成阶段的上胚层细胞的特征。fPSCs 可以从不同的小鼠 ESCs、原肠胚前期/早期上胚层和诱导性 PSCs 中建立。与原肠胚前期/早期上胚层相似，fPSCs 显示出形成多能性的转录组特征，与原始 ESCs 和初始 EpiSCs 不同。fPSCs 显示出 E6.5 上胚层的独特表观遗传状态，包括一组发育基因的超级二价性。就像原肠胚形成前的上胚层细胞一样，fPSCs 可以在体外有效地分化为三个胚层和原始生殖细胞 (PGCs)。因此，fPSCs 强调了使用 PSCs 来探索哺乳动物上胚层发育的可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/8089102/fd1fdb994433/41422_2021_477_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/8089102/fd1fdb994433/41422_2021_477_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/8089102/35fa02ea35dd/41422_2021_477_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/8089102/da1160efa35e/41422_2021_477_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/8089102/23dc85b023fd/41422_2021_477_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/8089102/d11e32e82914/41422_2021_477_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/8089102/fd1fdb994433/41422_2021_477_Fig7_HTML.jpg

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