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Lgr5 marks cycling, yet long-lived, hair follicle stem cells

Nature Genetics volume 40, pages 1291–1299 (2008)Cite this article

Abstract

In mouse hair follicles, a group of quiescent cells in the bulge is believed to have stem cell activity. Lgr5, a marker of intestinal stem cells, is expressed in actively cycling cells in the bulge and secondary germ of telogen hair follicles and in the lower outer root sheath of anagen hair follicles. Here we show that Lgr5+ cells comprise an actively proliferating and multipotent stem cell population able to give rise to new hair follicles and maintain all cell lineages of the hair follicle over long periods of time. Lgr5+ progeny repopulate other stem cell compartments in the hair follicle, supporting the existence of a stem or progenitor cell hierarchy. By marking Lgr5+ cells during trafficking through the lower outer root sheath, we show that these cells retain stem cell properties and contribute to hair follicle growth during the next anagen. Expression analysis suggests involvement of autocrine Hedgehog signaling in maintaining the Lgr5+ stem cell population.

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Figure 1: Lgr5 is expressed in basal cells of the bulge area and the ORS of the mouse hair follicle.
Figure 2: Lgr5+ cells are the primary proliferating cells at the onset of anagen and are distinct from LRCs.
Figure 3: The Lgr5+ cell population contains functional hair follicle stem cells.
Figure 4: The progeny of Lgr5+ cells contribute to all structures in hair follicles and maintain hair follicles over extended time periods.
Figure 5: Progeny of the Lgr5+ cells repopulate the permanent part, the bulge and the secondary germ of the hair follicle.
Figure 6: Lgr5+ cells show a pattern of stem cell gene expression, including markers of active Hh signaling.
Figure 7: Proposed model showing migration and repopulation of the hair follicle by Lgr5-expressing stem cells and their progeny.

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Acknowledgements

We thank D. Roop and W. Buitrago for help with setting up the keratinocyte transplantation assay; Å.-L. Dackland for help with cell sorting; Å. Bergström and I. Sur for contributions during work with animals and preparation of samples; and M. van den Born, M. Cozijnsen and H. Begthel for help with histological procedures. This work was supported by the Swedish Cancer Society (to R.T.), the Swedish Research Council (to R.T.), the National Institutes of Health (AR47898 and U01CA105491 to R.T.), Genmab BV (to H.C.), Koninklijke Nederlandse Akademie van Wetenschappen (to H.C.), Koningin Wilhelmina Fonds (to H.C.), the Louis Jeantet Foundation (to H.C.), an International Agency for Research on Cancer Research Training Fellowship (to V.J.), a Marie-Curie Intra-European Fellowship (to V.J.) and a fellowship from the Wenner-Gren Foundation (M.K.).

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Author notes

  1. Viljar Jaks, Nick Barker and Maria Kasper: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 57, Huddinge, Sweden

    Viljar Jaks, Maria Kasper & Rune Toftgård

  2. University of Tartu, Institute of Molecular and Cell Biology and Estonian Biocentre, Riia 23, Tartu, 51010, Estonia

    Viljar Jaks

  3. Hubrecht Institute, Uppsalalaan 8, Utrecht, 3584CT, The Netherlands

    Nick Barker, Johan H van Es, Hugo J Snippert & Hans Clevers

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  1. Viljar Jaks
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Correspondence to Hans Clevers or Rune Toftgård.

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Jaks, V., Barker, N., Kasper, M. et al. Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat Genet 40, 1291–1299 (2008). https://doi.org/10.1038/ng.239

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