BMI1 enables interspecies chimerism with human pluripotent stem cells

Ke Huang, Yanling Zhu, Yanlin Ma, Bentian Zhao, Nana Fan, Yuhang Li, Hong Song, Shilong Chu, Zhen Ouyang, Quanjun Zhang, Qi Xing, Chengdan Lai, Nan Li, Tian Zhang, Jiaming Gu, Baoqiang Kang, Yongli Shan, Keyu Lai, Wenhao Huang, Yuchan Mai, Qing Wang, Jinbing Li, Aiping Lin, Yanqi Zhang, Xiaofen Zhong, Baojian Liao, Liangxue Lai, Jiekai Chen, Duanqing Pei and Guangjin Pan ()
Additional contact information
Ke Huang: Guangzhou Medical University
Yanling Zhu: Guangzhou Medical University
Yanlin Ma: Hainan Medical University
Bentian Zhao: Guangzhou Medical University
Nana Fan: Guangzhou Medical University
Yuhang Li: Guangzhou Medical University
Hong Song: Guangzhou Medical University
Shilong Chu: Guangzhou Medical University
Zhen Ouyang: Guangzhou Medical University
Quanjun Zhang: Guangzhou Medical University
Qi Xing: Guangzhou Medical University
Chengdan Lai: Guangzhou Medical University
Nan Li: Guangzhou Medical University
Tian Zhang: Guangzhou Medical University
Jiaming Gu: Guangzhou Medical University
Baoqiang Kang: Guangzhou Medical University
Yongli Shan: Guangzhou Medical University
Keyu Lai: Guangzhou Medical University
Wenhao Huang: Guangzhou Medical University
Yuchan Mai: Guangzhou Medical University
Qing Wang: Guangzhou Medical University
Jinbing Li: Guangzhou Medical University
Aiping Lin: Guangzhou Medical University
Yanqi Zhang: Guangzhou Medical University
Xiaofen Zhong: Guangzhou Medical University
Baojian Liao: Guangzhou Medical University
Liangxue Lai: Guangzhou Medical University
Jiekai Chen: Guangzhou Medical University
Duanqing Pei: Guangzhou Medical University
Guangjin Pan: Guangzhou Medical University

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Human pluripotent stem cells (hPSCs) exhibit very limited contribution to interspecies chimeras. One explanation is that the conventional hPSCs are in a primed state and so unable to form chimeras in pre-implantation embryos. Here, we show that the conventional hPSCs undergo rapid apoptosis when injected into mouse pre-implantation embryos. While, forced-expression of BMI1, a polycomb factor in hPSCs overcomes the apoptosis and enables hPSCs to integrate into mouse pre-implantation embryos and subsequently contribute to chimeras with both embryonic and extra-embryonic tissues. In addition, BMI1 also enables hPSCs to integrate into pre-implantation embryos of other species, such as rabbit and pig. Notably, BMI1 high expression and anti-apoptosis are also indicators for naïve hPSCs to form chimera in mouse embryos. Together, our findings reveal that the apoptosis is an initial barrier in interspecies chimerism using hPSCs and provide a rational to improve it.

Date: 2018
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DOI: 10.1038/s41467-018-07098-w

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