IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50551-2.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50551-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50551-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Javier Rodríguez-Ubreva & Anna Arutyunyan & Marc Jan Bonder & Lucía Del Pino-Molina & Stephen J. Clark & Carlos de la Calle-Fabregat & Luz Garcia-Alonso & Louis-François Handfield & Laura Ciudad & Edu, 2022. "Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Jin Ming & Lihui Lin & Jiajun Li & Linlin Wu & Shicai Fang & Tao Huang & Yu Fu & Dong Liu & Wenhui Zhang & Chen Li & Yongzheng Yang & Yi Huang & Yue Qin & Junqi Kuang & Xingnan Huang & Liman Guo & Xia, 2024. "Cell fate decision by a morphogen-transcription factor-chromatin modifier axis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Zhaowei Yu & Qi Wang & Qichen Zhang & Yawen Tian & Guo Yan & Jidong Zhu & Guangya Zhu & Yong Zhang, 2024. "Decoding the genomic landscape of chromatin-associated biomolecular condensates," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Timothy D. Arthur & Jennifer P. Nguyen & Agnieszka D’Antonio-Chronowska & Hiroko Matsui & Nayara S. Silva & Isaac N. Joshua & André D. Luchessi & William W. Young Greenwald & Matteo D’Antonio & Martin, 2024. "Complex regulatory networks influence pluripotent cell state transitions in human iPSCs," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    5. Swarnendu Tripathi & Hazheen K. Shirnekhi & Scott D. Gorman & Bappaditya Chandra & David W. Baggett & Cheon-Gil Park & Ramiz Somjee & Benjamin Lang & Seyed Mohammad Hadi Hosseini & Brittany J. Pioso &, 2023. "Defining the condensate landscape of fusion oncoproteins," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    6. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50551-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.