TY - JOUR
T1 - Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo
AU - Tan, Tao
AU - Wu, Jun
AU - Si, Chenyang
AU - Dai, Shaoxing
AU - Zhang, Youyue
AU - Sun, Nianqin
AU - Zhang, E.
AU - Shao, Honglian
AU - Si, Wei
AU - Yang, Pengpeng
AU - Wang, Hong
AU - Chen, Zhenzhen
AU - Zhu, Ran
AU - Kang, Yu
AU - Hernandez-Benitez, Reyna
AU - Martinez Martinez, Llanos
AU - Nuñez Delicado, Estrella
AU - Berggren, W. Travis
AU - Schwarz, May
AU - Ai, Zongyong
AU - Li, Tianqing
AU - Rodriguez Esteban, Concepcion
AU - Ji, Weizhi
AU - Niu, Yuyu
AU - Izpisua Belmonte, Juan Carlos
N1 - Funding Information:
Special thanks to the Stanford University Research Ethics Program for helpful discussions and feedback during the protocol review process. We would like to thank David O’Keefe for his critical reading of this manuscript and invaluable comments. This work was supported by grants from the National Key Research and Development Program ( 2018YFA0801400 and 2016YFA0101401 ), the National Natural Science Foundation of China ( 81760271 and 31660346 ), Major Basic Research Project of Science and Technology of Yunnan ( 2017ZF028 and 202001BC070001 ), Key Projects of Basic Research Program in Yunnan Province ( 2017FA010 ), High-level Talent Cultivation Support Plan of Yunnan Province and Yunnan Fundamental Research Projects ( 2019FB050 ), UCAM , and The Moxie Foundation .
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/4/15
Y1 - 2021/4/15
N2 - 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.
AB - 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.
KW - ex-vivo-cultured mokey embryos
KW - human extended pluripotent stem cells
KW - human-monkey chimeric embryo
KW - interspecies chimera
KW - pluripotent stem cell
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U2 - 10.1016/j.cell.2021.03.020
DO - 10.1016/j.cell.2021.03.020
M3 - Article
C2 - 33861963
AN - SCOPUS:85104054838
SN - 0092-8674
VL - 184
SP - 2020-2032.e14
JO - Cell
JF - Cell
IS - 8
ER -