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

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 transplantati...

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Published inCell 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
LanguageEnglish
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
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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. [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.
AbstractList 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.
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.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.
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.
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.
Author Rodriguez Esteban, Concepcion
Zhang, Youyue
Nuñez Delicado, Estrella
Hernandez-Benitez, Reyna
Berggren, W. Travis
Ji, Weizhi
Zhu, Ran
Wu, Jun
Dai, Shaoxing
Chen, Zhenzhen
Deng, Hongkui
Si, Wei
Sun, Nianqin
Yang, Pengpeng
Izpisua Belmonte, Juan Carlos
Shao, Honglian
Zhang, E
Si, Chenyang
Martinez Martinez, Llanos
Schwarz, May
Ai, Zongyong
Li, Tianqing
Wang, Hong
Kang, Yu
Niu, Yuyu
Tan, Tao
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33861963$$D View this record in MEDLINE/PubMed
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IngestDate Fri Jul 11 07:34:24 EDT 2025
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Issue 8
Keywords human-monkey chimeric embryo
human extended pluripotent stem cells
interspecies chimera
pluripotent stem cell
ex-vivo-cultured mokey embryos
Language English
License Copyright © 2021 Elsevier Inc. All rights reserved.
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SSID ssj0008555
Score 2.6001372
Snippet Interspecies chimera formation with human pluripotent stem cells (hPSCs) represents a necessary alternative to evaluate hPSC pluripotency in vivo and might...
Interspecies chimera formation with human pluripotent stem cells (hPSCs) represents a necessary alternative to evaluate hPSC pluripotency in vivo and might...
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SubjectTerms 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
Title Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo
URI https://dx.doi.org/10.1016/j.cell.2021.03.020
https://www.ncbi.nlm.nih.gov/pubmed/33861963
https://www.proquest.com/docview/2514597718
https://www.proquest.com/docview/2551913604
Volume 184
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