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Status |
Public on Jan 12, 2016 |
Title |
Beta-catenin stabilization of skin fibroblasts causes fibrotic lesions by preventing adipocyte differentiation of the reticular dermis |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
The Wnt/alpha-catenin pathway plays a central role in epidermal homeostasis and regeneration but how it affects fibroblast fate decisions is unknown. Here, we investigated the effect of targeted alpha-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of Sca1- and Sca1+ neonatal fibroblasts, from upper and lower dermis respectively, confirmed that Sca1+ cells had a pre-adipocyte signature and revealed differential expression of Wnt/alpha‐catenin-associated genes. By targeting all fibroblasts or selectively targeting Dlk1+ lower dermal fibroblasts, we found that -catenin stabilization between 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/alpha-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases.
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Overall design |
The dermis was separated from back skin of PDGFRAeGFP postnatal pups (P2) by incubation with thermolysin (0.25 mg/ml) (Sigma T7902) overnight at 4° and further processed as previously described (Collins et al., 2011). Cells were labeled in PBS + 10% FBS TruStain fcX anti-mouse blocking buffer with the following antibodies: anti-mouse Ly-6A/E (Sca-1)-Alexa Fluor-700 17. Two populations of cells were collected in triplicate. The PDGFRaH2BeGFP/Sca1- and the PDGFRaH2BeGFP/Sca1+. RNA was isolated and prepared for microarray analysis and hybridized to Affymetrix MG430.2A arrays. C, digested in DMEM + 10% FBS containing 2.5 mg/mL collagenase I (Gibco 17100- 017), and further processed
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Citation(s) |
26902921 |
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Submission date |
Jan 11, 2016 |
Last update date |
Feb 11, 2019 |
Contact name |
Ryan R Driskell |
E-mail(s) |
ryan.driskell@kcl.ac.uk
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Organization name |
King's College London
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Department |
Centre for Stem Cells and Regenerative Medicine
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Street address |
28th Floor Guys Tower
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City |
London |
ZIP/Postal code |
SE1 9RT |
Country |
United Kingdom |
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Platforms (1) |
GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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Samples (6)
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Relations |
BioProject |
PRJNA308498 |