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SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair

Author

Listed:
  • Qi Miao

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Matthew C. Hill

    (Baylor College of Medicine)

  • Fengju Chen

    (Baylor College of Medicine)

  • Qianxing Mo

    (Baylor College of Medicine
    H. Lee Moffitt Cancer Center)

  • Amy T. Ku

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

  • Carlos Ramos

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Elisabeth Sock

    (Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Véronique Lefebvre

    (Children’s Hospital of Philadelphia)

  • Hoang Nguyen

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

Abstract

Tissue injury induces changes in cellular identity, but the underlying molecular mechanisms remain obscure. Here, we show that upon damage in a mouse model, epidermal cells at the wound edge convert to an embryonic-like state, altering particularly the cytoskeletal/extracellular matrix (ECM) components and differentiation program. We show that SOX11 and its closest relative SOX4 dictate embryonic epidermal state, regulating genes involved in epidermal development as well as cytoskeletal/ECM organization. Correspondingly, postnatal induction of SOX11 represses epidermal terminal differentiation while deficiency of Sox11 and Sox4 accelerates differentiation and dramatically impairs cell motility and re-epithelialization. Amongst the embryonic genes reactivated at the wound edge, we identify fascin actin-bundling protein 1 (FSCN1) as a critical direct target of SOX11 and SOX4 regulating cell migration. Our study identifies the reactivated embryonic gene program during wound repair and demonstrates that SOX11 and SOX4 play a central role in this process.

Suggested Citation

  • Qi Miao & Matthew C. Hill & Fengju Chen & Qianxing Mo & Amy T. Ku & Carlos Ramos & Elisabeth Sock & Véronique Lefebvre & Hoang Nguyen, 2019. "SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair," Nature Communications, Nature, vol. 10(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11880-9
    DOI: 10.1038/s41467-019-11880-9
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    Cited by:

    1. Amos C. Lee & Yongju Lee & Ahyoun Choi & Han-Byoel Lee & Kyoungseob Shin & Hyunho Lee & Ji Young Kim & Han Suk Ryu & Hoe Suk Kim & Seung Yeon Ryu & Sangeun Lee & Jong-Ho Cheun & Duck Kyun Yoo & Sumin , 2022. "Spatial epitranscriptomics reveals A-to-I editome specific to cancer stem cell microniches," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Elena Spina & Julia Simundza & Angela Incassati & Anupama Chandramouli & Matthias C. Kugler & Ziyan Lin & Alireza Khodadadi-Jamayran & Christine J. Watson & Pamela Cowin, 2022. "Gpr125 is a unifying hallmark of multiple mammary progenitors coupled to tumor latency," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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