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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Seishima R,Leung C,Yada S,Murad KBA,Tan LT,Hajamohideen A,Tan SH,Itoh H,Murakami K,Ishida Y,Nakamizo S,Yoshikawa Y,Wong E,Barker Ndoi
10.1038/s41467-019-13363-3subject
Has Abstractpub_date
2019-11-26 00:00:00pages
5378issue
1issn
2041-1723pii
10.1038/s41467-019-13363-3journal_volume
10pub_type
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