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

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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
Early online date3 Jun 2019
DOIs
Publication statusPublished - Jun 2019

Keywords

  • Animals
  • Blastomeres/cytology
  • Cell Differentiation/genetics
  • Cell Lineage/genetics
  • Cellular Reprogramming/genetics
  • Embryonic Stem Cells/cytology
  • Germ Layers/growth & development
  • Humans
  • Induced Pluripotent Stem Cells/cytology
  • Mice
  • Pluripotent Stem Cells/cytology
  • Regenerative Medicine
  • Signal Transduction/genetics
  • Swine
  • Trophoblasts/cytology

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