BRN2 suppresses stress-induced hair greying
- 1Institut Curie
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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BibTeX
@misc{larue2026brn2,
title = {{BRN2 suppresses stress-induced hair greying}},
author = {L. Larue and J. H. RAYMOND and M. LE COZ and Z. AKTARY and M. POUTEAUX and M. HAMM and E. Sage and V. FAVAUDON and V. Petit and A. Bellacosa and C. R. Goding},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.754993},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.754993v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - BRN2 suppresses stress-induced hair greying
AU - L. Larue
AU - J. H. RAYMOND
AU - M. LE COZ
AU - Z. AKTARY
AU - M. POUTEAUX
AU - M. HAMM
AU - E. Sage
AU - V. FAVAUDON
AU - V. Petit
AU - A. Bellacosa
AU - C. R. Goding
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.754993
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.754993v1
AB - 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.
ER -