Long-term in vivo chimeric cells tracking in non-human primate  

作　　者：Junmo Wu Yu Kang Xiang Luo Shaoxing Dai Yuxi Shi Zhuoyao Li Zengli Tang Zhenzhen Chen Ran Zhu Pengpeng Yang Zifan Li Hong Wang Xinglong Chen Ziyi Zhao Weizhi ji Yuyu Niu 

机构地区：[1]State Key Laboratory of Primate Biomedical Research,Institute of Primate Translational Medicine,Kunming University of Science and Technology,Kunming 650500,China [2]Yunnan Key Laboratory of Primate Biomedical Research,Kunming 650500,China [3]Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming 650500,China

出　　处：《Protein & Cell》2024年第3期207-222,共16页蛋白质与细胞（英文版）

基　　金：supported by grants from the National Key R&D Program of China(2021YFA0805700 and 2021YFA1102000);the National Natural Science Foundation of China(U2102204);the Natural Science Foundation of Yunnan Province(202001BC070001 and 202102AA100053).

摘　　要：Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关 键 词：pluripotent stem cells bioluminescence imaging non-human primates 

分 类 号：Q24[生物学—细胞生物学] Q813