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Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration

Author

Listed:
  • Ryan C. Ransom

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Ava C. Carter

    (Stanford University)

  • Ankit Salhotra

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Tripp Leavitt

    (Stanford University School of Medicine)

  • Owen Marecic

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Matthew P. Murphy

    (Stanford University School of Medicine)

  • Michael L. Lopez

    (Stanford University School of Medicine)

  • Yuning Wei

    (Stanford University)

  • Clement D. Marshall

    (Stanford University School of Medicine)

  • Ethan Z. Shen

    (Stanford University School of Medicine)

  • Ruth Ellen Jones

    (Stanford University School of Medicine)

  • Amnon Sharir

    (University of California)

  • Ophir D. Klein

    (University of California
    University of California
    University of California, San Francisco)

  • Charles K. F. Chan

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Derrick C. Wan

    (Stanford University School of Medicine)

  • Howard Y. Chang

    (Stanford University
    Stanford University)

  • Michael T. Longaker

    (Stanford University School of Medicine
    Stanford University School of Medicine)

Abstract

During both embryonic development and adult tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. A thorough understanding of how stem cells in the skeleton interpret mechanical stimuli and enact regeneration would shed light on how forces are transduced to the nucleus in regenerative processes. Here we develop a genetically dissectible mouse model of mandibular distraction osteogenesis—which is a process that is used in humans to correct an undersized lower jaw that involves surgically separating the jaw bone, which elicits new bone growth in the gap. We use this model to show that regions of newly formed bone are clonally derived from stem cells that reside in the skeleton. Using chromatin and transcriptional profiling, we show that these stem-cell populations gain activity within the focal adhesion kinase (FAK) signalling pathway, and that inhibiting FAK abolishes new bone formation. Mechanotransduction via FAK in skeletal stem cells during distraction activates a gene-regulatory program and retrotransposons that are normally active in primitive neural crest cells, from which skeletal stem cells arise during development. This reversion to a developmental state underlies the robust tissue growth that facilitates stem-cell-based regeneration of adult skeletal tissue.

Suggested Citation

  • Ryan C. Ransom & Ava C. Carter & Ankit Salhotra & Tripp Leavitt & Owen Marecic & Matthew P. Murphy & Michael L. Lopez & Yuning Wei & Clement D. Marshall & Ethan Z. Shen & Ruth Ellen Jones & Amnon Shar, 2018. "Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration," Nature, Nature, vol. 563(7732), pages 514-521, November.
    • Handle: RePEc:nat:nature:v:563:y:2018:i:7732:d:10.1038_s41586-018-0650-9
    DOI: 10.1038/s41586-018-0650-9
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    Cited by:

    1. Shuyi Wu & Shulu Luo & Zongheng Cen & Qianqian Li & Luwei Li & Weiran Li & Zhike Huang & Wenyi He & Guobin Liang & Dingcai Wu & Minghong Zhou & Yan Li, 2024. "All-in-one porous membrane enables full protection in guided bone regeneration," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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