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

• Published in: Cell Vol. 184; no. 8; pp. 2020 - 2032.e14
• Main Authors: Tan, Tao, Wu, Jun, Si, Chenyang, Dai, Shaoxing, Zhang, Youyue, Sun, Nianqin, Zhang, E, Shao, Honglian, Si, Wei, Yang, Pengpeng, Wang, Hong, Chen, Zhenzhen, Zhu, Ran, Kang, Yu, Hernandez-Benitez, Reyna, Martinez Martinez, Llanos, Nuñez Delicado, Estrella, Berggren, W. Travis, Schwarz, May, Ai, Zongyong, Li, Tianqing, Deng, Hongkui, Rodriguez Esteban, Concepcion, Ji, Weizhi, Niu, Yuyu, Izpisua Belmonte, Juan Carlos
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.04.2021
• Subjects: chimerism; evolution; ex-vivo-cultured mokey embryos; genetic distance; human development; human extended pluripotent stem cells; human-monkey chimeric embryo; humans; interspecies chimera; Macaca fascicularis; medicine; mice; monkeys; pluripotent stem cell; swine; human-monkey chimeric embryo; human extended pluripotent stem cells; interspecies chimera; pluripotent stem cell; ex-vivo-cultured mokey embryos
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2021.03.020

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. [Display omitted] •Generation of human-monkey chimeric embryos ex vivo with hEPSCs•hEPSCs differentiated into hypoblast and epiblast lineages•scRNA-seq analyses revealed developmental trajectories of human and monkey cells•The approach may allow for enhancing chimerism between evolutionarily distant species Human cells, in the form of extended pluripotent stem cells, have the ability to contribute to both embryonic and extra-embryonic lineages in ex-vivo-cultured monkey embryos.