BRN2 suppresses stress-induced hair greying

Larue, L.; RAYMOND, J. H.; LE COZ, M.; AKTARY, Z.; POUTEAUX, M.; HAMM, M.; Sage, E.; FAVAUDON, V.; Petit, V.; Bellacosa, A.; Goding, C. R.

doi:10.64898/2026.09.28.754993

bioRxiv · 10.64898/2026.09.28.754993

BRN2 suppresses stress-induced hair greying

Larue, L.·RAYMOND, J. H.·LE COZ, M.·AKTARY, Z.·POUTEAUX, M.·HAMM, M.·Sage, E.·FAVAUDON, V.·Petit, V.·Bellacosa, A.·Goding, C. R.

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Abstract

Adult stem cells maintain tissue homeostasis and regenerative capacity, but mechanisms preserving their integrity under stress remain incompletely understood. Here, we identify BRN2 (POU3F2), a POU-domain transcription factor, as a regulator of melanocyte lineage homeostasis and response to genotoxic stress. Single-cell transcriptomic analyses identified Brn2 among transcription factors preferentially active in melanocyte stem cells (McSCs), with BRN2 activity declining with age in human hair follicle melanocytic cells. Melanocyte-specific Brn2 deletion increased melanocyte differentiation and accumulation in the hair bulb, while downregulating DNA-repair and chromosome-maintenance programs. Despite these changes, Brn2 loss caused neither spontaneous hair greying nor detectable McSC depletion under steady-state conditions. Following ionizing radiation, however, Brn2-deficient cells showed altered DNA-damage responses, reduced mitotic signatures, increased p53 and p21, and enhanced melanocytic differentiation. Irradiated Brn2-deficient mice developed rapid, dose-dependent, permanent hair depigmentation associated with McSC and melanocyte depletion. Thus, BRN2 links POU-dependent transcriptional control to stem-cell resilience under genotoxic stress, preserving melanocyte regenerative capacity and protecting against irradiation-induced hair greying.

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Larue, L., RAYMOND, J. H., LE COZ, M., AKTARY, Z., POUTEAUX, M., HAMM, M., Sage, E., FAVAUDON, V., Petit, V., Bellacosa, A., Goding, C. R.. 2026-10-04. BRN2 suppresses stress-induced hair greying. https://doi.org/10.64898/2026.09.28.754993

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