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

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

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吉林大学; 西北农林科技大学; 中国科学院研究生院; 深圳华大基因研究院; 中国科学院

摘要

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.

关键词

GROUND-STATE RNA-SEQ NAIVE PLURIPOTENCY DNA DEMETHYLATION CYNOMOLGUS MONKEY MACAQUE MONKEYS GENERATION DERIVATION TRANSCRIPTOME ESTABLISHMENT