人源扩展多能干细胞对体外猴胚胎的嵌合贡献。

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

机构信息

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

出版信息

Cell. 2021 Apr 15;184(8):2020-2032.e14. doi: 10.1016/j.cell.2021.03.020.

DOI:10.1016/j.cell.2021.03.020

PMID:33861963

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.

摘要

人多能干细胞（hPSCs）与其他物种的嵌合体形成代表了一种在体内评估 hPSC 多能性的必要替代方法，并且可能构成各种再生医学应用的有前途的策略，包括用于移植的器官和组织的产生。使用小鼠和猪胚胎的研究表明，hPSCs 在与人类进化距离较远的物种中不会强烈地促进嵌合体形成。我们研究了人扩展多能干细胞（hEPSCs）在体外培养的食蟹猴（Macaca fascicularis）胚胎中的嵌合能力。我们证明 hEPSCs 在猴子胚胎内存活、增殖并产生了几个围植入期和早期植入后细胞谱系。我们还揭示了种间串扰的信号事件，这些事件可能有助于塑造嵌合胚胎中人类和猴子细胞的独特发育轨迹。这些结果可能有助于更好地理解人类早期发育和灵长类动物进化，并开发在进化距离较远的物种中提高人类嵌合率的策略。