PT  - JOURNAL ARTICLE
AU  - Adèle Mauroux
AU  - Pauline Joncour
AU  - Benjamin Gillet
AU  - Sandrine Hughes
AU  - Corinne Ardidie-Robouant
AU  - Laëtitia Marchand
AU  - Athanasia Liabotis
AU  - Philippe Mailly
AU  - Catherine Monnot
AU  - Stephane Germain
AU  - Sylvie Bordes
AU  - Brigitte Closs
AU  - Florence Ruggiero
AU  - Laurent Muller
TI  - Papillary and Reticular Fibroblasts Generate Distinct Microenvironments that Differentially Impact Angiogenesis
AID  - 10.1101/2020.11.29.402594
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.29.402594
4099  - http://biorxiv.org/content/early/2020/11/29/2020.11.29.402594.short
4100  - http://biorxiv.org/content/early/2020/11/29/2020.11.29.402594.full
AB  - Papillary and reticular dermis show distinct extracellular matrix (ECM) and vascularization, and fibroblasts isolated from these compartments have different gene expression patterns and behaviour in vitro. However, due to lack of relevant models, the contribution of skin fibroblast sub-populations to vascularization remains unknown. We thus cultured human papillary and reticular fibroblasts as cell sheets. Differential transcriptomic analysis was performed by RNA sequencing to characterize their microenvironment. Bioinformatic analysis revealed that each fibroblast population expressed specific angiogenesis and matrisome gene expression signatures resulting in specific ECM that differed both in composition and structure. The impact of secreted and ECM-bound factors was then assessed using 3D angiogenesis assays. When co-cultivated with endothelial cells, the papillary and reticular microenvironments induced the formation of distinct capillary networks mimicking the characteristics of vasculature of native dermis subcompartments (vessel diameter and density, number of branch points). Whereas conditioned media of papillary fibroblasts displayed intrinsic high angiogenic potential, reticular ones only contributed to capillary formation induced by exogenous VEGF. These results show that skin fibroblast populations regulate angiogenesis via both secreted and ECM-bound factors. Our work emphasizes the importance of papillary and reticular fibroblasts, not only for modelling dermis microenvironment but also for its vascularization.Competing Interest StatementAM, LM, SB, and BC are employees of SILAB. FR and LM declare the receipt of a grant from SILAB. PJ, BG, SH, CA, AL, PM, CM and SG state no conflict of interest