Establishment of porcine and human expanded potential stem cells

Xuefei Gao, Monika Nowak-imialek, Xi Chen, Dongsheng Chen, Doris Herrmann, Degong Ruan, Andy Chun Hang Chen, Melanie A. Eckersley-maslin, Shakil Ahmad, Yin Lau Lee, Toshihiro Kobayashi, David Ryan, Jixing Zhong, Jiacheng Zhu, Jian Wu, Guocheng Lan, Stoyan Petkov, Jian Yang, Liliana Antunes, Lia S. CamposBeiyuan Fu, Shengpeng Wang, Yu Yong, Xiaomin Wang, Song-guo Xue, Liangpeng Ge, Zuohua Liu, Yong Huang, Tao Nie, Peng Li, Donghai Wu, Duanqing Pei, Yi Zhang, Liming Lu, Fengtang Yang, Susan J. Kimber, Wolf Reik, Xiangang Zou, Zhouchun Shang, Liangxue Lai, Azim Surani, Patrick P. L. Tam, Asif Ahmed, William Shu Biu Yeung, Sarah A. Teichmann, Heiner Niemann, Pentao Liu

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)687-699
Number of pages13
JournalNature Cell Biology
Volume21
Issue number6
DOIs
Publication statusPublished - 3 Jun 2019

Bibliographical note

© 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)).

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    Gao, X., Nowak-imialek, M., Chen, X., Chen, D., Herrmann, D., Ruan, D., Chen, A. C. H., Eckersley-maslin, M. A., Ahmad, S., Lee, Y. L., Kobayashi, T., Ryan, D., Zhong, J., Zhu, J., Wu, J., Lan, G., Petkov, S., Yang, J., Antunes, L., ... Liu, P. (2019). Establishment of porcine and human expanded potential stem cells. Nature Cell Biology, 21(6), 687-699. https://doi.org/10.1038/s41556-019-0333-2