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Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration

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Listed:
  • Hirohito Abo

    (Georgia State University)

  • Benoit Chassaing

    (Georgia State University
    Georgia State University
    INSERM, U1016
    Université de Paris)

  • Akihito Harusato

    (Georgia State University)

  • Miguel Quiros

    (University of Michigan)

  • Jennifer C. Brazil

    (University of Michigan)

  • Vu L. Ngo

    (Georgia State University)

  • Emilie Viennois

    (Georgia State University)

  • Didier Merlin

    (Georgia State University
    Atlanta Veterans Affairs Medical Center)

  • Andrew T. Gewirtz

    (Georgia State University)

  • Asma Nusrat

    (University of Michigan)

  • Timothy L. Denning

    (Georgia State University)

Abstract

Gut microbiota and their metabolites are instrumental in regulating intestinal homeostasis. However, early-life microbiota associated influences on intestinal development remain incompletely understood. Here we demonstrate that co-housing of germ-free (GF) mice with specific-pathogen free (SPF) mice at weaning (exGF) results in altered intestinal gene expression. Our results reveal that one highly differentially expressed gene, erythroid differentiation regulator-1 (Erdr1), is induced during development in SPF but not GF or exGF mice and localizes to Lgr5+ stem cells and transit amplifying (TA) cells. Erdr1 functions to induce Wnt signaling in epithelial cells, increase Lgr5+ stem cell expansion, and promote intestinal organoid growth. Additionally, Erdr1 accelerates scratch-wound closure in vitro, increases Lgr5+ intestinal stem cell regeneration following radiation-induced injury in vivo, and enhances recovery from dextran sodium sulfate (DSS)-induced colonic damage. Collectively, our findings indicate that early-life microbiota controls Erdr1-mediated intestinal epithelial proliferation and regeneration in response to mucosal damage.

Suggested Citation

  • Hirohito Abo & Benoit Chassaing & Akihito Harusato & Miguel Quiros & Jennifer C. Brazil & Vu L. Ngo & Emilie Viennois & Didier Merlin & Andrew T. Gewirtz & Asma Nusrat & Timothy L. Denning, 2020. "Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14258-z
    DOI: 10.1038/s41467-019-14258-z
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