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Live imaging of stem cell and progeny behaviour in physiological hair-follicle regeneration

Nature volume 487, pages 496–499 (2012)Cite this article

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Abstract

Tissue development and regeneration depend on cell–cell interactions and signals that target stem cells and their immediate progeny1. However, the cellular behaviours that lead to a properly regenerated tissue are not well understood. Using a new, non-invasive, intravital two-photon imaging approach we study physiological hair-follicle regeneration over time in live mice. By these means we have monitored the behaviour of epithelial stem cells and their progeny2,3,4 during physiological hair regeneration and addressed how the mesenchyme5 influences their behaviour. Consistent with earlier studies6, stem cells are quiescent during the initial stages of hair regeneration, whereas the progeny are more actively dividing. Moreover, stem cell progeny divisions are spatially organized within follicles. In addition to cell divisions, coordinated cell movements of the progeny allow the rapid expansion of the hair follicle. Finally, we show the requirement of the mesenchyme for hair regeneration through targeted cell ablation and long-term tracking of live hair follicles. Thus, we have established an in vivo approach that has led to the direct observation of cellular mechanisms of growth regulation within the hair follicle and that has enabled us to precisely investigate functional requirements of hair-follicle components during the process of physiological regeneration.

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Figure 1: Cell divisions are spatially regulated in the hair follicle at the beginning of a new growth.
Figure 2: The stem cell progeny compartment undergoes morphological reorganization during growth.
Figure 3: Ablation of the mesenchymal dermal papilla impairs initiation of hair regeneration.
Figure 4: The cellular mechanisms that participate in hair regeneration.

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Acknowledgements

We are grateful to A. Horwich, V. Reinke and A. Giraldez for critical discussion of the work. We thank S. King for feedback on the manuscript, and E. Fuchs for the K14H2BGFP, Lef1RFP and pTREH2BGFP mice and A. Glick for the K5tta mice. P.R. is supported by the James Hudson Brown – Alexander Brown Coxe postdoctoral fellowship. G.Z. is a New York Stem Cell Foundation–Druckenmiller Fellow. E.D. is supported by the Cell and Molecular Biology Training Grant of the National Institute of General Medical Sciences, US National Institutes of Health, Public Health Service. This work was supported in part by the American Skin Association, the American Cancer Society and the Yale Rheumatologic Disease Research Core Center grant NIH P30AR053495.

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Author notes

  1. Elizabeth R. Deschene and Giovanni Zito: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics, Department of Dermatology, Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine, New Haven, 06510, Connecticut, USA

    Panteleimon Rompolas, Elizabeth R. Deschene, Giovanni Zito, Ichiko Saotome & Valentina Greco

  2. Department of Laboratory Medicine, Yale School of Medicine, New Haven, 06510, Connecticut, USA

    David G. Gonzalez & Ann M. Haberman

Authors
  1. Panteleimon Rompolas
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  2. Elizabeth R. Deschene
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Contributions

Author Contributions P.R. and V.G. designed experiments and wrote the manuscript, and P.R. performed the experiments and analysed the data. E.D. performed two-photon laser-scanning timelapses. G.Z. performed immunostainings. I.S. set up the mouse colonies and staining protocols. D.G. and A.H. assisted on initial intravital imaging set-up. D.G. performed data analysis.

Corresponding author

Correspondence to Valentina Greco.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-9 and Legends for Supplementary Movies 1-9. (PDF 8970 kb)

Supplementary Movie 1

This movie shows serial optical sections of in vivo mouse skin imaging (see Supplementary information file for full legend). (MOV 2393 kb)

Supplementary Movie 2

This movie shows cell divisions visualized in real-time in the hair follicle stem cell progeny compartment (see Supplementary information file for full legend). (MOV 6223 kb)

Supplementary Movie 3

This movie shows cell divisions visualized in real-time in the hair follicle stem cell progeny compartment (see Supplementary information file for full legend). (MOV 1679 kb)

Supplementary Movie 4

This movie shows cell divisions visualized in real-time in the hair follicle stem cell compartment (see Supplementary information file for full legend). (MOV 4920 kb)

Supplementary Movie 5

This movie shows rapid downward extension of the progeny compartment of the hair follicle during growth (see Supplementary information file for full legend). (MOV 1479 kb)

Supplementary Movie 6

This movie shows rapid downward extension of the progeny compartment of the hair follicle during growth (see Supplementary information file for full legend). (MOV 488 kb)

Supplementary Movie 7

This movie shows re-organization of the progeny compartment of the hair follicle around the mesenchyme during growth (see Supplementary information file for full legend). (MOV 3636 kb)

Supplementary Movie 8

This movie shows downward migration of nuclei in the hair follicle (see Supplementary information file for full legend). (MOV 1356 kb)

Supplementary Movie 9

This movie shows upward migration of nuclei in the hair follicle bulge (see Supplementary information file for full legend). (MOV 1376 kb)

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Rompolas, P., Deschene, E., Zito, G. et al. Live imaging of stem cell and progeny behaviour in physiological hair-follicle regeneration. Nature 487, 496–499 (2012). https://doi.org/10.1038/nature11218

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