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Engineering mouse cell fate controller by rational design

Author

Listed:
  • Tao Huang

    (Zhejiang University
    Westlake University)

  • Dong Liu

    (Westlake University)

  • Xiaomin Wang

    (Westlake University)

  • Junqi Kuang

    (Westlake University
    Westlake Institute for Advanced Study
    Westlake Laboratory of Life Sciences and Biomedicine)

  • Manqi Wu

    (Westlake University)

  • Beibei Wang

    (Westlake University)

  • Zechuan Liang

    (Zhejiang University
    Westlake University)

  • Yixin Fan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Bo Chen

    (Westlake University
    Westlake Institute for Advanced Study)

  • Zhaoyi Ma

    (Zhejiang University
    Westlake University)

  • Yu Fu

    (Westlake University)

  • Wenhui Zhang

    (Zhejiang University
    Westlake University)

  • Jin Ming

    (Westlake University
    Westlake Institute for Advanced Study)

  • Yue Qin

    (Westlake University
    Westlake Institute for Advanced Study)

  • Chengchen Zhao

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Key Laboratory of Biomedical Intelligent Computing Technology of Zhejiang Province)

  • Bo Wang

    (Westlake University
    Key Laboratory of Biomedical Intelligent Computing Technology of Zhejiang Province
    Zhejiang University of Science and Technology School of Information and Electronic Engineering)

  • Duanqing Pei

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine)

Abstract

Cell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller NanogBiD, fusing BiD or BRG1 interacting domain of SS18 with Nanog. NanogBiD promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog, resulting in precocious activation of multiple genes including Sall4, miR-302, Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.

Suggested Citation

  • Tao Huang & Dong Liu & Xiaomin Wang & Junqi Kuang & Manqi Wu & Beibei Wang & Zechuan Liang & Yixin Fan & Bo Chen & Zhaoyi Ma & Yu Fu & Wenhui Zhang & Jin Ming & Yue Qin & Chengchen Zhao & Bo Wang & Du, 2024. "Engineering mouse cell fate controller by rational design," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50551-2
    DOI: 10.1038/s41467-024-50551-2
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    References listed on IDEAS

    as
    1. Yael Costa & Junjun Ding & Thorold W. Theunissen & Francesco Faiola & Timothy A. Hore & Pavel V. Shliaha & Miguel Fidalgo & Arven Saunders & Moyra Lawrence & Sabine Dietmann & Satyabrata Das & Dana N., 2013. "NANOG-dependent function of TET1 and TET2 in establishment of pluripotency," Nature, Nature, vol. 495(7441), pages 370-374, March.
    2. Bo Wang & Chen Li & Jin Ming & Linlin Wu & Shicai Fang & Yi Huang & Lihui Lin & He Liu & Junqi Kuang & Chengchen Zhao & Xingnan Huang & Huijian Feng & Jing Guo & Xuejie Yang & Liman Guo & Xiaofei Zhan, 2023. "The NuRD complex cooperates with SALL4 to orchestrate reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Junqi Kuang & Ziwei Zhai & Pengli Li & Ruona Shi & Wenjing Guo & Yuxiang Yao & Jing Guo & Guoqing Zhao & Jiangpin He & Shuyang Xu & Chuman Wu & Shengyong Yu & Chunhua Zhou & Linlin Wu & Yue Qin & Baom, 2021. "SS18 regulates pluripotent-somatic transition through phase separation," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Yanli Cheng & Zhongtian Shen & Yaqi Gao & Feilong Chen & Huisha Xu & Qinling Mo & Xinlei Chu & Chang-liang Peng & Takese T. McKenzie & Bridgitte E. Palacios & Jian Hu & Hao Zhou & Jiafu Long, 2022. "Phase transition and remodeling complex assembly are important for SS18-SSX oncogenic activity in synovial sarcomas," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
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