Basement membrane components define the microenvironment of aggregated fibroblasts in the skin and support their aggregation in vitro

While its aggregated configuration is critical for its function, the mechanism promoting and maintaining this organization has remained unclear. Here, we show that human DP cells are embedded in a basement membrane (BM)-like extracellular matrix (ECM) rather than in conventional interstitial fibrillar ECM, such as collagen I. This BM-like ECM occupies the intercellular space as a diffuse, mesh-like structure, with minimal cell‒cell adhesion.

DP cells interact with specific laminin isoforms containing α1, α2 or α4 chains via integrin α7β1, resulting in weak adhesiveness. In vitro, a BM extract-based matrix, Matrigel, supports both the formation and maintenance of DP aggregates and is associated with improved DP-marker gene expression, but collagen I gel promotes their dispersion in an α1β1 integrin-dependent manner. These findings highlight a BM-like ECM niche as a key determinant of DP cohesion.