期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 136, 期 6, 页码 1130-1142出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2016.01.036
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资金
- Medical Research Council
- Wellcome Trust
- European Molecular Biology Organization
- Federation of European Biochemical Societies
- Guy's & St. Thomas' National Health Service (NHS) Foundation Trust
- Medical Research Council [G1100073] Funding Source: researchfish
- MRC [G1100073] Funding Source: UKRI
The Wnt/beta-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 beta-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/beta-catenin associated genes. By targeting all fibroblasts or selectively targeting Dlk1(+) lower dermal fibroblasts, we found that beta-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/beta-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases.
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