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Lgr5 marks stem/progenitor cells in ovary and tubal epithelia

Nature Cell Biology volume 16, pages 745757 (2014) | Download Citation

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.

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Acknowledgements

We thank A. Ong, A. Wong and A. Tan for technical assistance, G. Wright and J. Lim for imaging assistance, S. Mustafah for FACS experiments, and D. Tan for technical expertise and manuscript proofreading. We also thank M. Choolani and B. Pang for providing human material and critical discussions before publication. N.B. is supported by the Agency for Science, Technology and Research (A*STAR), Singapore.

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Affiliations

  1. A-STAR Institute of Medical Biology, 8A Biomedical Grove, 06-06 Immunos, 138648, Singapore

    • Annie Ng
    • , Shawna Tan
    • , Gurmit Singh
    • , Pamela Rizk
    • , Yada Swathi
    • , Marc Leushacke
    •  & Nick Barker
  2. Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore

    • Tuan Zea Tan
    •  & Ruby Yun-Ju Huang
  3. Department of Obstetrics & Gynaecology, National University Hospital, 119228, Singapore

    • Ruby Yun-Ju Huang
  4. Centre for Regenerative Medicine, 47 Little France Crescent, University of Edinburgh, EH16 4TJ, UK

    • Nick Barker
  5. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117596, Singapore

    • Nick Barker

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Contributions

A.N. designed and performed experiments, analysed data and wrote the manuscript. S.T., P.R. and Y.S. performed microarray experiments and bioinformatics analyses. G.S. performed mouse injections. T.Z.T. and R.Y-J.H. conducted the gene set enrichment analyses. M.L. performed proliferation experiments and provided technical expertise. N.B. supervised the project, analysed the data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Nick Barker.

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https://doi.org/10.1038/ncb3000

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