Volume 31, No 5, May 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 5, May 2021: 526-541   |  Open Access

ORIGINAL ARTICLES

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

Xiaoxiao Wang¹ , Yunlong Xiang² , Yang Yu¹ , Ran Wang³ , Yu Zhang⁴ , Qianhua Xu⁴ , Hao Sun¹ , Zhen-Ao Zhao¹ , Xiangxiang Jiang¹ , Xiaoqing Wang¹ , Xukun Lu¹ , Dandan Qin¹ , Yujun Quan¹ , Jiaqi Zhang¹ , Ng Shyh-Chang¹ , Hongmei Wang¹ , Naihe Jing^3,5 , Wei Xie^4,* , Lei Li^1,*

¹State 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
²Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
³State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
⁴Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
⁵Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China
Correspondence: Wei Xie(121@tsinghua.edu.cn)Lei Li(lil@ioz.ac.cn)

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.

https://doi.org/10.1038/s41422-021-00477-x

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