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A dermal niche for multipotent adult skin-derived precursor cells

Nature Cell Biology volume 6, pages 1082–1093 (2004)Cite this article

An Addendum to this article was published on 01 May 2005

Abstract

A fundamental question in stem cell research is whether cultured multipotent adult stem cells represent endogenous multipotent precursor cells. Here we address this question, focusing on SKPs, a cultured adult stem cell from the dermis that generates both neural and mesodermal progeny. We show that SKPs derive from endogenous adult dermal precursors that exhibit properties similar to embryonic neural-crest stem cells. We demonstrate that these endogenous SKPs can first be isolated from skin during embryogenesis and that they persist into adulthood, with a niche in the papillae of hair and whisker follicles. Furthermore, lineage analysis indicates that both hair and whisker follicle dermal papillae contain neural-crest-derived cells, and that SKPs from the whisker pad are of neural-crest origin. We propose that SKPs represent an endogenous embryonic precursor cell that arises in peripheral tissues such as skin during development and maintains multipotency into adulthood.

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Figure 1: SKPs express markers of embryonic neural crest and differentiate into peripheral neurons and Schwann cells.
Figure 2: SKPs migrate like neural crest cells when transplanted in ovo.
Figure 3: Multipotent endogenous SKPs are abundant in skin during late embryogenesis and persist into adulthood.
Figure 4: Expression of SKP transcription factors is localized to the follicle papillae of dorsal hair follicles and is hair-cycle dependent.
Figure 5: Neural-crest-derived facial dermis dynamically expresses SKP markers, which become progressively restricted to follicle papillae of vibrissae and hair follicles.
Figure 6: Adult whisker papillae contain SKP-like cells.
Figure 7: Hair and whisker follicle papillae contain neural crest-derived cells.
Figure 8: SKPs derived from facial skin are of neural-crest origin.

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Acknowledgements

We thank A. Aumont, Y. Wang-Ninio, A. Rioux-Taché for technical support; the Miller and Kaplan laboratories for valuable discussion of this work; and A. Nagy for providing mice. This work was funded by grants from The Canadian Stem Cell Network and the Canadian Institutes of Health Resesarch (CIHR) to F.D.M., from CIHR to C.C.H., from the National Institutes of Health to P.A.L., from the National Sciences and Engineering Council (NSERC) to V.R. and the National Cancer Institute of Canada to D.R.K.. K.J.L.F. was funded by fellowships from the CIHR/Canadian Neurotrauma Research Program and Restracomp, K.M.S. from CIHR and Restracomp, F.B.H. from CIHR, J.B. from the Parkinsons Foundation of Canada and N.R.K. from the Christopher Reeves Paralysis Foundation.

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Author notes

  1. Karl J. L. Fernandes and Ian A. McKenzie: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cancer Research, University of Toronto, Toronto, M5G 1X8, Ontario, Canada

    Karl J. L. Fernandes, Kristen M. Smith & David R. Kaplan

  2. Department of Developmental Biology, Hospital For Sick Children Research Institute, University of Toronto, Toronto, M5G 1X8, Ontario, Canada

    Karl J. L. Fernandes, Ian A. McKenzie, Pleasantine Mill, Kristen M. Smith, Mahnaz Akhavan, Fanie Barnabé-Heider, Jeff Biernaskie, Nao R. Kobayashi, Jean G. Toma, David R. Kaplan, Chi-Chung Hui & Freda D. Miller

  3. Departments of Medical and Molecular Genetics, University of Toronto, Toronto, M5G 1X8, Ontario, Canada

    Pleasantine Mill, David R. Kaplan, Chi-Chung Hui & Freda D. Miller

  4. Department of Physiology, University of Toronto, Toronto, M5G 1X8, Ontario, Canada

    Freda D. Miller

  5. Department of Neurology and Neurosurgery, McGill University, Montreal, H3A 2B4, Quebec, Canada

    Ian A. McKenzie & Fanie Barnabé-Heider

  6. Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, 19104-6058, PA, USA

    Patricia A. Labosky

  7. Department of Anatomy and Neurobiology, Dalhousie University, Halifax, B3H 1X5, Nova Scotia, Canada

    Adrienne Junek & Victor Rafuse

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Competing interests

David Kaplan and Freda Miller are consultants for, and shareholders of, Aegera Therapeutics Inc., who have licensed patents dealing with SKPs from their owner, McGill University.

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Fernandes, K., McKenzie, I., Mill, P. et al. A dermal niche for multipotent adult skin-derived precursor cells. Nat Cell Biol 6, 1082–1093 (2004). https://doi.org/10.1038/ncb1181

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