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BMI1 enables interspecies chimerism with human pluripotent stem cells

Author

Listed:
  • Ke Huang

    (Guangzhou Medical University
    Chinese Academy of Sciences
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Yanling Zhu

    (Guangzhou Medical University
    Chinese Academy of Sciences
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Yanlin Ma

    (Hainan Medical University)

  • Bentian Zhao

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Nana Fan

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Yuhang Li

    (Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Hong Song

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Shilong Chu

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Zhen Ouyang

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Quanjun Zhang

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Qi Xing

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Chengdan Lai

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Nan Li

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Tian Zhang

    (Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jiaming Gu

    (Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Baoqiang Kang

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Yongli Shan

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Keyu Lai

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Wenhao Huang

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Yuchan Mai

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Qing Wang

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Jinbing Li

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Aiping Lin

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Yanqi Zhang

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Xiaofen Zhong

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Baojian Liao

    (Guangzhou Medical University
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Liangxue Lai

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Jiekai Chen

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Duanqing Pei

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Guangjin Pan

    (Guangzhou Medical University
    Chinese Academy of Sciences
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

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.

Suggested Citation

  • 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 , 2018. "BMI1 enables interspecies chimerism with human pluripotent stem cells," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07098-w
    DOI: 10.1038/s41467-018-07098-w
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    Cited by:

    1. Yueli Yang & Wenqi Jia & Zhiwei Luo & Yunpan Li & Hao Liu & Lixin Fu & Jinxiu Li & Yu Jiang & Junjian Lai & Haiwei Li & Babangida Jabir Saeed & Yi Zou & Yuan Lv & Liang Wu & Ting Zhou & Yongli Shan & , 2024. "VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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