Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nature. 2013 Dec 12;504(7479):277-81. doi: 10.1038/nature12783.

Distinct fibroblast lineages determine dermal architecture in skin development and repair.

Author information

  • 11] Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge CB2 1QR, UK [2] Centre for Stem Cells and Regenerative Medicine, King's College London, 28th floor, Tower Wing, Guy's Hospital, London SE1 9RT, UK.
  • 21] Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge CB2 1QR, UK [2] Centre for Stem Cells and Regenerative Medicine, King's College London, 28th floor, Tower Wing, Guy's Hospital, London SE1 9RT, UK [3].
  • 31] Centre for Stem Cells and Regenerative Medicine, King's College London, 28th floor, Tower Wing, Guy's Hospital, London SE1 9RT, UK [2] Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK [3].
  • 4Department of Physics, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK.
  • 5Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
  • 6Institut Clinique de la Souris, Parc d'Innovation, 67404 Illkrich-Graffenstaden, Cedex, France.
  • 7Centre for Stem Cells and Regenerative Medicine, King's College London, 28th floor, Tower Wing, Guy's Hospital, London SE1 9RT, UK.

Abstract

Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibres of the extracellular matrix (ECM). Even within a single tissue, fibroblasts exhibit considerable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different environmental factors. Here we show, using transplantation assays and lineage tracing in mice, that the fibroblasts of skin connective tissue arise from two distinct lineages. One forms the upper dermis, including the dermal papilla that regulates hair growth and the arrector pili muscle, which controls piloerection. The other forms the lower dermis, including the reticular fibroblasts that synthesize the bulk of the fibrillar ECM, and the preadipocytes and adipocytes of the hypodermis. The upper lineage is required for hair follicle formation. In wounded adult skin, the initial wave of dermal repair is mediated by the lower lineage and upper dermal fibroblasts are recruited only during re-epithelialization. Epidermal β-catenin activation stimulates the expansion of the upper dermal lineage, rendering wounds permissive for hair follicle formation. Our findings explain why wounding is linked to formation of ECM-rich scar tissue that lacks hair follicles. They also form a platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease.

PMID:
24336287
[PubMed - indexed for MEDLINE]
PMCID:
PMC3868929
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk