RESEARCH ARTICLE

Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs

  • Rui Fu 1,2 ,
  • Dawei Yu 1,2 ,
  • Jilong Ren 1,2 ,
  • Chongyang Li 1,2,3 ,
  • Jing Wang 1,2,3 ,
  • Guihai Feng 1,2 ,
  • Xuepeng Wang 1,2 ,
  • Haifeng Wan 1,2 ,
  • Tianda Li 1,2 ,
  • Libin Wang 1,2 ,
  • Ying Zhang 1,2,3 ,
  • Tang Hai , 1,2 ,
  • Wei Li , 1,2,3 ,
  • Qi Zhou , 1,2,3
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  • 1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
  • 2. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
  • 3. University of Chinese Academy of Sciences, Beijing 100049, China

Received date: 06 Aug 2019

Accepted date: 26 Oct 2019

Published date: 15 Feb 2020

Copyright

2019 The Author(s)

Abstract

Blastocyst complementation by pluripotent stem cell (PSC) injection is believed to be the most promising method to generate xenogeneic organs. However, ethical issues prevent the study of human chimeras in the late embryonic stage of development. Primate embryonic stem cells (ESCs), which have similar pluripotency to human ESCs, are a good model for studying interspecies chimerism and organ generation. However, whether primate ESCs can be used in xenogenous grafts remains unclear. In this study, we evaluated the chimeric ability of cynomolgus monkey (Macaca fascicularis) ESCs (cmESCs) in pigs, which are excellent hosts because of their many similarities to humans. We report an optimized culture medium that enhanced the anti-apoptotic ability of cmESCs and improved the development of chimeric embryos, in which domesticated cmESCs (D-ESCs) injected into pig blastocysts differentiated into cells of all three germ layers. In addition, we obtained two neonatal interspecies chimeras, in which we observed tissue-specific D-ESC differentiation. Taken together, the results demonstrate the capability of D-ESCs to integrate and differentiate into functional cells in a porcine model, with a chimeric ratio of 0.001–0.0001 in different neonate tissues. We believe this work will facilitate future developments in xenogeneic organogenesis, bringing us one step closer to producing tissue-specific functional cells and organs in a large animal model through interspecies blastocyst complementation.

Cite this article

Rui Fu , Dawei Yu , Jilong Ren , Chongyang Li , Jing Wang , Guihai Feng , Xuepeng Wang , Haifeng Wan , Tianda Li , Libin Wang , Ying Zhang , Tang Hai , Wei Li , Qi Zhou . Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs[J]. Protein & Cell, 2020 , 11(2) : 97 -107 . DOI: 10.1007/s13238-019-00676-8

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