BMP6 coordinates dermal papilla and epithelial cell states for hair follicle engineering and regeneration

Siegfried, L. G., Zhou, L., Wang, J., Hahn, J. M., Dodson, C., Choi, Y. S., Babitt, J. L., Supp, D. M., Millar, S. E., Andl, T., et al.

10.64898/2026.09.30.755211 · was preprinted

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Abstract

Human hair follicle engineering is hindered by the rapid loss of inductive competence in culture-expanded dermal papilla (DP) fibroblasts. Here we show that bone morphogenetic protein 6 (BMP6) maintains and restores DP-associated characteristics while promoting follicular epithelial differentiation by restricting keratinocyte (KC) proliferation and inducing hair follicle-associated marker expression. Human follicle transcriptomics further linked BMP activity to DP identity and follicular epithelial differentiation. Genetic mouse studies demonstrate that BMP6 in Sox2-positive DP cells contributes to normal anagen onset, progression, and maintenance. Gain- and loss-of-function studies in KC-DP organoids show that BMP6 promotes epithelial-mesenchymal organization and spatially patterned follicular structures. In vivo, topical BMP6 promotes anagen onset, whereas BMP6 overexpression restores the hair follicle-generating capacity of late-passage human DP fibroblasts. Together, these findings identify BMP6 as a compartment-dependent regulator that enhances human DP competence and promotes epithelial differentiation, supporting regenerative hair follicle formation and engineering with culture-expanded DP cells.

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biorxiv v1 2026-10-02 source ↗

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