Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo

Tao Tan, Jun Wu, Chenyang Si, Shaoxing Dai, Youyue Zhang, Nianqin Sun, E. Zhang, Honglian Shao, Wei Si, Pengpeng Yang, Hong Wang, Zhenzhen Chen, Ran Zhu, Yu Kang, Reyna Hernandez-Benitez, Llanos Martinez Martinez, Estrella Nuñez Delicado, W. Travis Berggren, May Schwarz, Zongyong AiTianqing Li, Concepcion Rodriguez Esteban, Weizhi Ji, Yuyu Niu, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticlepeer-review

Abstract

Interspecies chimera formation with human pluripotent stem cells (hPSCs) represents a necessary alternative to evaluate hPSC pluripotency in vivo and might constitute a promising strategy for various regenerative medicine applications, including the generation of organs and tissues for transplantation. Studies using mouse and pig embryos suggest that hPSCs do not robustly contribute to chimera formation in species evolutionarily distant to humans. We studied the chimeric competency of human extended pluripotent stem cells (hEPSCs) in cynomolgus monkey (Macaca fascicularis) embryos cultured ex vivo. We demonstrate that hEPSCs survived, proliferated, and generated several peri- and early post-implantation cell lineages inside monkey embryos. We also uncovered signaling events underlying interspecific crosstalk that may help shape the unique developmental trajectories of human and monkey cells within chimeric embryos. These results may help to better understand early human development and primate evolution and develop strategies to improve human chimerism in evolutionarily distant species.

Original languageEnglish (US)
Pages (from-to)2020-2032.e14
JournalCell
Volume184
Issue number8
DOIs
StatePublished - Apr 15 2021
Externally publishedYes

Keywords

  • ex-vivo-cultured mokey embryos
  • human extended pluripotent stem cells
  • human-monkey chimeric embryo
  • interspecies chimera
  • pluripotent stem cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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