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Neonatal Wnt-dependent Lgr5 positive stem cells are essential for uterine gland development

Author

Listed:
  • Ryo Seishima

    (A*STAR Institute of Medical Biology)

  • Carly Leung

    (A*STAR Institute of Medical Biology)

  • Swathi Yada

    (A*STAR Institute of Medical Biology)

  • Katzrin Bte Ahmed Murad

    (A*STAR Institute of Medical Biology)

  • Liang Thing Tan

    (A*STAR Institute of Medical Biology)

  • Amin Hajamohideen

    (A*STAR Institute of Medical Biology)

  • Si Hui Tan

    (A*STAR Institute of Medical Biology)

  • Hideki Itoh

    (A*STAR Skin Research Institute of Singapore)

  • Kazuhiro Murakami

    (Kanazawa University)

  • Yoshihiro Ishida

    (Kyoto University)

  • Satoshi Nakamizo

    (A*STAR Skin Research Institute of Singapore)

  • Yusuke Yoshikawa

    (A*STAR Institute of Medical Biology)

  • Esther Wong

    (A*STAR Institute of Medical Biology)

  • Nick Barker

    (A*STAR Institute of Medical Biology
    Kanazawa University
    Nanyang Technological University)

Abstract

Wnt signaling is critical for directing epithelial gland development within the uterine lining to ensure successful gestation in adults. Wnt-dependent, Lgr5-expressing stem/progenitor cells are essential for the development of glandular epithelia in the intestine and stomach, but their existence in the developing reproductive tract has not been investigated. Here, we employ Lgr5-2A-EGFP/CreERT2/DTR mouse models to identify Lgr5-expressing cells in the developing uterus and to evaluate their stem cell identity and function. Lgr5 is broadly expressed in the uterine epithelium during embryogenesis, but becomes largely restricted to the tips of developing glands after birth. In-vivo lineage tracing/ablation/organoid culture assays identify these gland-resident Lgr5high cells as Wnt-dependent stem cells responsible for uterine gland development. Adjacent Lgr5neg epithelial cells within the neonatal glands function as essential niche components to support the function of Lgr5high stem cells ex-vivo. These findings constitute a major advance in our understanding of uterine development and lay the foundations for investigating potential contributions of Lgr5+ stem/progenitor cells to uterine disorders.

Suggested Citation

  • Ryo Seishima & Carly Leung & Swathi Yada & Katzrin Bte Ahmed Murad & Liang Thing Tan & Amin Hajamohideen & Si Hui Tan & Hideki Itoh & Kazuhiro Murakami & Yoshihiro Ishida & Satoshi Nakamizo & Yusuke Y, 2019. "Neonatal Wnt-dependent Lgr5 positive stem cells are essential for uterine gland development," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13363-3
    DOI: 10.1038/s41467-019-13363-3
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    Cited by:

    1. Rong Li & Tianyuan Wang & Ryan M. Marquardt & John P. Lydon & San-Pin Wu & Francesco J. DeMayo, 2023. "TRIM28 modulates nuclear receptor signaling to regulate uterine function," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Lana Kostic & Carly Leung & Katzrin Ahmad Murad & Snezhina Kancheva & Stefano Perna & Bernett Lee & Nick Barker, 2024. "Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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