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Nat Cell Biol. 2017 Jun;19(6):603-613. doi: 10.1038/ncb3532. Epub 2017 May 15.

Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of stem cell properties.

Author information

1
King's College London Centre for Stem Cells and Regenerative Medicine, 28th Floor, Tower Wing, Guy's Campus, Great Maze Pond, London SE1 9RT, UK.
2
Cancer Research UK Cambridge Research Institute, Cambridge CB2 0RE, UK.
3
Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy.
4
VIB Center for Inflammation Research, Department of Biomedical Molecular Biology (Ghent University), B-9052 Ghent, Belgium.
5
European Bioinformatics Institute and Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SD, UK.
6
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
7
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK.
8
Hubrecht Institute, KNAW and UMC Utrecht, 3584CT Utrecht, The Netherlands.
9
Radboud Institute for Molecular Life Sciences, Department of Molecular Developmental Biology, Radboud University, Nijmegen, TheĀ Netherlands.

Abstract

The epidermis is maintained by multiple stem cell populations whose progeny differentiate along diverse, and spatially distinct, lineages. Here we show that the transcription factor Gata6 controls the identity of the previously uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream transcription factor network that specifies a lineage switch between sebocytes and SD cells. During wound healing differentiated Gata6+ cells migrate from the SD into the interfollicular epidermis and dedifferentiate, acquiring the ability to undergo long-term self-renewal and differentiate into a much wider range of epidermal lineages than in undamaged tissue. Our data not only demonstrate that the structural and functional complexity of the junctional zone is regulated by Gata6, but also reveal that dedifferentiation is a previously unrecognized property of post-mitotic, terminally differentiated cells that have lost contact with the basement membrane. This resolves the long-standing debate about the contribution of terminally differentiated cells to epidermal wound repair.

PMID:
28504705
DOI:
10.1038/ncb3532
[Indexed for MEDLINE]
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