Abstract
The ovary surface epithelium (OSE) undergoes ovulatory tear and remodelling throughout life. Resident stem cells drive such tissue homeostasis in many adult epithelia, but their existence in the ovary has not been definitively proven. Lgr5 marks stem cells in multiple epithelia. Here we use reporter mice and single-molecule fluorescent in situ hybridization to document candidate Lgr5(+) stem cells in the mouse ovary and associated structures. Lgr5 is broadly expressed during ovary organogenesis, but becomes limited to the OSE in neonate life. In adults, Lgr5 expression is predominantly restricted to proliferative regions of the OSE and mesovarian-fimbria junctional epithelia. Using in vivo lineage tracing, we identify embryonic and neonate Lgr5(+) populations as stem/progenitor cells contributing to the development of the OSE cell lineage, as well as epithelia of the mesovarian ligament and oviduct/fimbria. Adult Lgr5(+) populations maintain OSE homeostasis and ovulatory regenerative repair in vivo. Thus, Lgr5 marks stem/progenitor cells of the ovary and tubal epithelia.
MeSH Terms
Adult Stem Cells/metabolism
Animals
Animals, Newborn
Cell Lineage/genetics
Embryonic Stem Cells/metabolism
Epithelial Cells/cytology,metabolism
Fallopian Tubes/cytology,growth & development,metabolism
Female
Gene Expression
Genetic Markers
Homeostasis/genetics
Humans
In Situ Hybridization, Fluorescence
Mice
Mice, Transgenic
Models, Biological
Ovary/cytology,growth & development,metabolism
Receptors, G-Protein-Coupled/genetics
Regeneration/genetics
Transcriptome
Chemicals
Genetic Markers
LGR5 protein, human
Lgr5 protein, mouse
Receptors, G-Protein-Coupled
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ng Annie
A-STAR Institute of Medical Biology, 8A Biomedical Grove, 06-06 Immunos, 138648, Singapore.
Tan Shawna
A-STAR Institute of Medical Biology, 8A Biomedical Grove, 06-06 Immunos, 138648, Singapore.
Singh Gurmit
A-STAR Institute of Medical Biology, 8A Biomedical Grove, 06-06 Immunos, 138648, Singapore.
Rizk Pamela
A-STAR Institute of Medical Biology, 8A Biomedical Grove, 06-06 Immunos, 138648, Singapore.
Swathi Yada
A-STAR Institute of Medical Biology, 8A Biomedical Grove, 06-06 Immunos, 138648, Singapore.
Tan Tuan Zea
Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore.
Huang Ruby Yun-Ju
1] Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore [2] Department of Obstetrics &Gynaecology, National University Hospital, 119228, Singapore.
Leushacke Marc
A-STAR Institute of Medical Biology, 8A Biomedical Grove, 06-06 Immunos, 138648, Singapore.
Barker Nick
1] A-STAR Institute of Medical Biology, 8A Biomedical Grove, 06-06 Immunos, 138648, Singapore [2] Centre for Regenerative Medicine, 47 Little France Crescent, University of Edinburgh, EH16 4TJ, UK [3] Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117596, Singapore.
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