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具有来自胚胎干细胞高贡献的嵌合猴的活体出生。

Live birth of chimeric monkey with high contribution from embryonic stem cells.

作者信息

Cao Jing, Li Wenjuan, Li Jie, Mazid Md Abdul, Li Chunyang, Jiang Yu, Jia Wenqi, Wu Liang, Liao Zhaodi, Sun Shiyu, Song Weixiang, Fu Jiqiang, Wang Yan, Lu Yong, Xu Yuting, Nie Yanhong, Bian Xinyan, Gao Changshan, Zhang Xiaotong, Zhang Liansheng, Shang Shenshen, Li Yunpan, Fu Lixin, Liu Hao, Lai Junjian, Wang Yang, Yuan Yue, Jin Xin, Li Yan, Liu Chuanyu, Lai Yiwei, Shi Xuyang, Maxwell Patrick H, Xu Xun, Liu Longqi, Poo Muming, Wang Xiaolong, Sun Qiang, Esteban Miguel A, Liu Zhen

机构信息

Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.

Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.

出版信息

Cell. 2023 Nov 9;186(23):4996-5014.e24. doi: 10.1016/j.cell.2023.10.005.

Abstract

A formal demonstration that mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency is the generation of chimeric animals through early embryo complementation with homologous cells. Whereas such naive pluripotency has been well demonstrated in rodents, poor chimerism has been achieved in other species including non-human primates due to the inability of the donor cells to match the developmental state of the host embryos. Here, we have systematically tested various culture conditions for establishing monkey naive embryonic stem cells and optimized the procedures for chimeric embryo culture. This approach generated an aborted fetus and a live chimeric monkey with high donor cell contribution. A stringent characterization pipeline demonstrated that donor cells efficiently (up to 90%) incorporated into various tissues (including the gonads and placenta) of the chimeric monkeys. Our results have major implications for the study of primate naive pluripotency and genetic engineering of non-human primates.

摘要

通过早期胚胎与同源细胞互补产生嵌合体动物,是对哺乳动物多能干细胞具有植入前胚胎细胞样(原始)多能性的一种正式证明。虽然这种原始多能性在啮齿动物中已得到充分证明,但由于供体细胞无法与宿主胚胎的发育状态相匹配,在包括非人灵长类动物在内的其他物种中,嵌合率一直很低。在这里,我们系统地测试了各种培养条件以建立猴原始胚胎干细胞,并优化了嵌合胚胎培养程序。这种方法产生了一个流产胎儿和一只供体细胞贡献度高的活嵌合猴。严格的鉴定流程表明,供体细胞有效地(高达90%)整合到了嵌合猴的各种组织(包括性腺和胎盘)中。我们的研究结果对灵长类动物原始多能性的研究以及非人灵长类动物的基因工程具有重要意义。

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