Differential Expression of Insulin-Like Growth Factor 1 and Wnt Family Member 4 Correlates With Functional Heterogeneity of Human Dermal Fibroblasts.
IGF1
WNT4
cell culture
epidermis
fibroblasts
signalling
skin
α-SMA
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2021
2021
Historique:
received:
10
11
2020
accepted:
09
03
2021
entrez:
23
4
2021
pubmed:
24
4
2021
medline:
24
4
2021
Statut:
epublish
Résumé
Although human dermis contains distinct fibroblast subpopulations, the functional heterogeneity of fibroblast lines from different donors is under-appreciated. We identified one commercially sourced fibroblast line (c64a) that failed to express α-smooth muscle actin (α-SMA), a marker linked to fibroblast contractility, even when treated with transforming growth factor-β1 (TGF-β1). Gene expression profiling identified insulin-like growth factor 1 (IGF1) as being expressed more highly, and Asporin (ASPN) and Wnt family member 4 (WNT4) expressed at lower levels, in c64a fibroblasts compared to three fibroblast lines that had been generated in-house, independent of TGF-β1 treatment. TGF-β1 increased expression of C-X-C motif chemokine ligand 1 (CXCL1) in c64a cells to a greater extent than in the other lines. The c64a gene expression profile did not correspond to any dermal fibroblast subpopulation identified by single-cell RNAseq of freshly isolated human skin cells. In skin reconstitution assays, c64a fibroblasts did not support epidermal stratification as effectively as other lines tested. In fibroblast lines generated in-house, shRNA-mediated knockdown of IGF1 increased α-SMA expression without affecting epidermal stratification. Conversely, WNT4 knockdown had no consistent effect on α-SMA expression, but increased the ability of fibroblasts to support epidermal stratification. Thus, by comparing the properties of different lines of cultured dermal fibroblasts, we have identified IGF1 and WNT4 as candidate mediators of two distinct dermal functions: myofibroblast formation and epidermal maintenance.
Identifiants
pubmed: 33889572
doi: 10.3389/fcell.2021.628039
pmc: PMC8056032
doi:
Types de publication
Journal Article
Langues
eng
Pagination
628039Informations de copyright
Copyright © 2021 Culley, Louis, Philippeos, Oulès, Tihy, Segal, Hyliands, Jenkins, Bhogal, Siow and Watt.
Déclaration de conflit d'intérêts
DH, GJ, and RB are employees of Unilever. FW is on secondment as Executive Chair, Medical Research Council. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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