The dermal papilla (DP), a specialized fibroblast aggregate in mammalian skin, plays a pivotal role in hair follicle development and regeneration through epithelial‒mesenchymal interactions. While its aggregated configuration is critical for its function, the mechanism 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. These fibroblasts interact with specific laminin isoforms containing α1, α2 or α4 chains via integrin α7β1, resulting in weak adhesiveness. In vitro, DP spheroids remained aggregated in a BM extract-based matrix, Matrigel, but dispersed in collagen I gel in an α1β1 integrin-dependent manner. Our findings suggest that the BM components within DP aggregates mediate cell‒ECM interactions and maintain the cohesive DP structure in the absence of strong cell‒cell contacts. These results reveal an unconventional role for the BM as an adhesive microenvironment that sustains fibroblast aggregation and offer a new perspective on mesenchymal tissue organization and in vitro culture substrates for DP cells.
Hiroki Machida, Jun Yokota, Hironobu Fujiwara (2026) Basement membrane components define the microenvironment of aggregated fibroblasts in the skin and support their aggregation in vitro., Matrix biology : journal of the International Society for Matrix Biology, pp. 102008
Published in 2026 Apr 17 (Electronic publication in April 17, 2026, midnight )
(Abstract) The dermal papilla (DP), a specialized fibroblast aggregate in mammalian skin, plays a pivotal role in hair follicle development and regeneration through epithelial‒mesenchymal interactions. 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 alpha1, alpha2 or alpha4 chains via integrin alpha7beta1, 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 alpha1beta1 integrin-dependent manner. These findings highlight a BM-like ECM niche as a key determinant of DP cohesion.