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J Invest Dermatol. 2016 Jun;136(6):1130-1142. doi: 10.1016/j.jid.2016.01.036. Epub 2016 Feb 20.

β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis.

Author information

1
Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK; Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
2
Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
3
Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
4
Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK. Electronic address: fiona.watt@kcl.ac.uk.

Abstract

The Wnt/β-catenin pathway plays a central role in epidermal homeostasis and regeneration, but how it affects fibroblast fate decisions is unknown. We investigated the effect of targeted β-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of stem cell antigen 1(-) (Sca1(-)) and Sca1(+) neonatal fibroblasts from upper and lower dermis, respectively, confirmed that Sca1(+) cells had a preadipocyte signature and showed differential expression of Wnt/β-catenin-associated genes. By targeting all fibroblasts or selectively targeting Dlk1(+) lower dermal fibroblasts, we found that β-catenin stabilization between developmental stages E16.5 and P2 resulted in a reduction in the dermal adipocyte layer with a corresponding increase in dermal fibrosis and an altered hair cycle. The fibrotic phenotype correlated with a reduction in the potential of Sca1(+) fibroblasts to undergo adipogenic differentiation ex vivo. Our findings indicate that Wnt/β-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases.

PMID:
26902921
PMCID:
PMC4874948
DOI:
10.1016/j.jid.2016.01.036
[Indexed for MEDLINE]
Free PMC Article

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