Improving Cell Survival in Injected Embryos Allows Primed Pluripotent Stem Cells to Generate Chimeric Cynomolgus Monkeys

Yu Kang; Zongyong Ai; Kui Duan; Chenyang Si; Yong Wang; Yun Zheng; Jingjing He; Yu Yin; Shumei Zhao; Baohua Niu; Xiaoqing Zhu; Li Liu; Lifeng Xiang; Linming Zhang; Yuyu Niu; Weizhi Ji; Tianqing Li

doi:10.1016/j.celrep.2018.11.001

Improving Cell Survival in Injected Embryos Allows Primed Pluripotent Stem Cells to Generate Chimeric Cynomolgus Monkeys

Cell Rep. 2018 Nov 27;25(9):2563-2576.e9. doi: 10.1016/j.celrep.2018.11.001.

Authors

Yu Kang¹, Zongyong Ai², Kui Duan¹, Chenyang Si¹, Yong Wang³, Yun Zheng¹, Jingjing He¹, Yu Yin¹, Shumei Zhao¹, Baohua Niu¹, Xiaoqing Zhu², Li Liu¹, Lifeng Xiang¹, Linming Zhang⁴, Yuyu Niu², Weizhi Ji², Tianqing Li⁵

Affiliations

¹ Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Provincial Academy of Science and Technology, Kunming, Yunnan 650500, China.
² Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Provincial Academy of Science and Technology, Kunming, Yunnan 650500, China; Kunming Enovate Institute of Bioscience, Kunming, Yunnan 650500, China.
³ Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
⁴ Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
⁵ Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Provincial Academy of Science and Technology, Kunming, Yunnan 650500, China; Kunming Enovate Institute of Bioscience, Kunming, Yunnan 650500, China. Electronic address: litq@lpbr.cn.

PMID: 30485820
DOI: 10.1016/j.celrep.2018.11.001

Abstract

Monkeys are an optimal model species for developing stem cell therapies. We previously reported generating chimeric cynomolgus monkey fetuses using dome-shaped embryonic stem cells (dESCs). However, conventional primed pluripotent stem cells (pPSCs) lack chimera competency. Here, by altering the media in which injected morulae are cultured, we observed increased survival of cynomolgus monkey primed ESCs, induced PSCs, and somatic cell nuclear transfer-derived ESCs, thereby enabling chimeric contributions with 0.1%-4.5% chimerism into the embryonic and placental tissues, including germ cell progenitors in chimeric monkeys. Mechanically, dESCs and pPSCs belong to different cell types and similarly express epiblast ontogenic genes. The host embryonic microenvironment could reprogram injected PSCs to embryonic-like cells. However, the reprogramming level and chimerism were associated with the cell state of injected PSCs. Our findings provide a method to understand pluripotency and broaden the use of embryonic chimeras for basic developmental biology research and regenerative medicine.

Keywords: chimeric monkey; dome-shape embryonic stem cells; embryonic microenvironment; monkey somatic cell nuclear transfer-derived embryonic stem cells; primed pluripotent stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Cell Survival
Cellular Microenvironment
Cellular Reprogramming
Chimerism*
Embryo Culture Techniques
Embryo, Mammalian / cytology*
Gene Expression Regulation
Injections*
Macaca fascicularis
Pluripotent Stem Cells / cytology*
Pluripotent Stem Cells / metabolism
Trophoblasts / cytology