Establishment of porcine and human expanded potential stem cells

Abstract

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.

Publication DOI: https://doi.org/10.1038/s41556-019-0333-2
Divisions: College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © The Author(s), under exclusive licence to Springer Nature Limited 2019. Funding: the Wellcome Trust (grant nos. 098051 and 206194) to the Sanger Institute and the University of Hong Kong internal funding (P. Liu); a Wellcome Trust Clinical PhD Fellowship for Academic Clinicians (D.J.R.); a PhD fellowship from the Portuguese Foundation for Science and Technology, FCT (grant no. SFRH/BD/84964/2012; L.A.); a Marie Sklodowska-Curie Individual Fellowship (M.A.E.-M.); the BBSRC (grant no. BB/K010867/1), Wellcome Trust (grant no. 095645/Z/11/Z), EU EpiGeneSys and BLUEPRINT (W.R.); a Chongqing Agriculture Development Grant (grant no. 17407 to L.P.G., Z.H.L. and Y.H.); REBIRTH project no. 9.1, Hannover Medical School (H.N.); Shuguang Planning of Shanghai Municipal Education Commission (grant no. 16SG14) and the National Key Research and Development Program (grant no. 2017YFA0104500; L. Lu); the China Postdoctoral Science Foundation (grant no. 2017M622795; D.C.); the Strategic Priority Research Program of CAS (grant nos. XDA16030503 and XDA16030501), the National Key Research and Development Program of China Stem Cell and Translational Research (grant no. 2017YFA0105103) and Key Research and Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (grant no. 2018GZR110104004; L.Lai); the Shenzhen Municipal Government of China (DRC-SZ [2016] 884; Z.S.); the NHMRC of Australia (Senior Principal Research Fellowship grant no. 1110751; P.P.L.T.); the GRF of Hong Kong (grant nos 17119117 and 17107915) and the National Natural Science Foundation (grant nos. 81671579 (L. Lu), 31471398 (W.S.B.Y.) and U1804281 (Y. Zhang)).
Uncontrolled Keywords: Cell Biology
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.natu ... 1556-019-0333-2 (Publisher URL)
PURE Output Type: Article
Published Date: 2019-06-03
Accepted Date: 2019-04-24
Authors: Gao, Xuefei
Nowak-imialek, Monika
Chen, Xi
Chen, Dongsheng
Herrmann, Doris
Ruan, Degong
Chen, Andy Chun Hang
Eckersley-maslin, Melanie A.
Ahmad, Shakil (ORCID Profile 0000-0002-9294-0475)
Lee, Yin Lau
Kobayashi, Toshihiro
Ryan, David
Zhong, Jixing
Zhu, Jiacheng
Wu, Jian
Lan, Guocheng
Petkov, Stoyan
Yang, Jian
Antunes, Liliana
Campos, Lia S.
Fu, Beiyuan
Wang, Shengpeng
Yong, Yu
Wang, Xiaomin
Xue, Song-guo
Ge, Liangpeng
Liu, Zuohua
Huang, Yong
Nie, Tao
Li, Peng
Wu, Donghai
Pei, Duanqing
Zhang, Yi
Lu, Liming
Yang, Fengtang
Kimber, Susan J.
Reik, Wolf
Zou, Xiangang
Shang, Zhouchun
Lai, Liangxue
Surani, Azim
Tam, Patrick P. L.
Ahmed, Asif (ORCID Profile 0000-0002-8755-8546)
Yeung, William Shu Biu
Teichmann, Sarah A.
Niemann, Heiner
Liu, Pentao

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