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.

Details

Title
BMI1 enables interspecies chimerism with human pluripotent stem cells
Author
Huang, Ke 1 ; Zhu, Yanling 2 ; Ma, Yanlin 3 ; Zhao, Bentian 4 ; Fan, Nana 4 ; Li, Yuhang 5 ; Song, Hong 4 ; Chu, Shilong 4 ; Ouyang, Zhen 4 ; Zhang, Quanjun 4 ; Xing, Qi 4 ; Lai, Chengdan 4 ; Li, Nan 4 ; Zhang, Tian 5 ; Gu, Jiaming 5 ; Kang, Baoqiang 4 ; Shan, Yongli 4 ; Lai, Keyu 4 ; Huang, Wenhao 4 ; Mai, Yuchan 4 ; Wang, Qing 4 ; Li, Jinbing 4 ; Lin, Aiping 4 ; Zhang, Yanqi 4 ; Zhong, Xiaofen 4 ; Liao, Baojian 6 ; Lai, Liangxue 4 ; Chen, Jiekai 4   VIAFID ORCID Logo  ; Pei, Duanqing 4 ; Pan, Guangjin 1 

1  Key Laboratory of Regenerative Biology of Chinese Academy of Sciences, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China; Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China 
2  Key Laboratory of Regenerative Biology of Chinese Academy of Sciences, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China; Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China 
3  Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, China 
4  Key Laboratory of Regenerative Biology of Chinese Academy of Sciences, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China 
5  Key Laboratory of Regenerative Biology of Chinese Academy of Sciences, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China 
6  Key Laboratory of Regenerative Biology of Chinese Academy of Sciences, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China 
Pages
1-11
Publication year
2018
Publication date
Nov 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-07098-w
ProQuest document ID
2130793336
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.