BMI1 enables interspecies chimerism with human pluripotent stem cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

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, Guangjin Pan

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. More... »

PAGES

4649

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-07098-w

DOI

http://dx.doi.org/10.1038/s41467-018-07098-w

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107969582

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30405129


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