Establishment of porcine and human expanded potential stem cells

Nat Cell Biol. 2019 Jun;21(6):687-699. doi: 10.1038/s41556-019-0333-2.

Xuefei Gao ¹ ², Monika Nowak-Imialek ³ ⁴, Xi Chen ², Dongsheng Chen ⁵ ⁶, Doris Herrmann ³ ⁴, Degong Ruan ¹ ⁷, Andy Chun Hang Chen ⁸, Melanie A Eckersley-Maslin ⁹, Shakil Ahmad ¹⁰, Yin Lau Lee ⁸, Toshihiro Kobayashi ¹¹, David Ryan ², Jixing Zhong ⁵ ⁶, Jiacheng Zhu ⁵ ⁶, Jian Wu ¹, Guocheng Lan ¹², Stoyan Petkov ³ ⁴ ¹³, Jian Yang ² ¹⁴, Liliana Antunes ², Lia S Campos ², Beiyuan Fu ², Shengpeng Wang ⁵ ⁶, Yu Yong ², Xiaomin Wang ⁷, Song-Guo Xue ¹⁵, Liangpeng Ge ¹⁶, Zuohua Liu ¹⁶, Yong Huang ¹⁶, Tao Nie ⁷, Peng Li ⁷, Donghai Wu ⁷, Duanqing Pei ⁷ ¹⁷, Yi Zhang ¹⁸, Liming Lu ¹⁹, Fengtang Yang ², Susan J Kimber ²⁰, Wolf Reik ⁹, Xiangang Zou ¹², Zhouchun Shang ⁵ ⁶, Liangxue Lai ⁷, Azim Surani ¹¹, Patrick P L Tam ²¹, Asif Ahmed ¹⁰, William Shu Biu Yeung ⁸, Sarah A Teichmann ², Heiner Niemann ²² ²³ ²⁴, Pentao Liu ²⁵ ²⁶

Affiliations

1 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Stem Cell and Regenerative Medicine Consortium, Pokfulam, Hong Kong.
2 The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
3 Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut (FLI), Mariensee, Neustadt, Germany.
4 REBIRTH Centre of Excellence, Hannover Medical School, Hannover, Germany.
5 BGI-Shenzhen, Shenzhen, China.
6 China National GeneBank, BGI-Shenzhen, Shenzhen, China.
7 Key Laboratory of Regenerative Biology of Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
8 Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
9 Epigenetics Programme, Babraham Institute, Babraham Research Campus, Cambridge, UK.
10 Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, UK.
11 Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.
12 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
13 German Primate Center, Platform Degenerative Diseases, Gottingen, Germany.
14 Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
15 Center for Reproductive Medicine, Shanghai East Hospital, School of Medicine, Tong Ji University, Shanghai, China.
16 Chongqing Academy of Animal Sciences and Key Laboratory of Pig Industry Sciences, Department of Agriculture, Chongqing, China.
17 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China.
18 Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Henan, China.
19 Institute of Immunology, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
20 Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.
21 Embryology Unit, Children's Medical Research Institute and School of Medical Sciences, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
22 Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut (FLI), Mariensee, Neustadt, Germany. [email protected].
23 REBIRTH Centre of Excellence, Hannover Medical School, Hannover, Germany. [email protected].
24 Hannover Medical School (MHH), TwinCore, Hannover, Germany. [email protected].
25 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Stem Cell and Regenerative Medicine Consortium, Pokfulam, Hong Kong. [email protected].
26 The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. [email protected].

PMID: 31160711 DOI: 10.1038/s41556-019-0333-2

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.

Products

Cat. No.

Product Name

Description

Target

Research Area
HY-12299G

WH-4-023 (GMP)

Lck/Src Inhibitor

Src

Cancer

Name
Email *

	Sorry, but the email address you supplied was invalid.