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

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 Yoshikawa, Esther Wong and Nick Barker ()
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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

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13363-3

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