BRN2 preserves the melanocyte lineage following ionizing radiation
- 1Institut Curie
Abstract
Adult stem cells maintain tissue homeostasis, but mechanisms preserving their integrity under stress remain incompletely understood. Here, we identify BRN2 (POU3F2), previously implicated in neuronal development, reprogramming of fibroblasts to neurons and in melanoma proliferation, migration and DNA-damage responses, as a key guardian of melanocyte stem cells. Remarkably, we reveal that while Brn2-deficient mice maintain their McSC compartment and normal pigmentation for up to 95 weeks, in contrast, rapid, dose-dependent, permanent hair depigmentation associated with the disappearance of detectable McSCs and differentiated melanocytes occurs in Brn2 KO mice exposed to ionizing radiation but not in WT mice. Importantly, our results indicate that in human follicular melanocytes BRN2 activity in melanocyte stem cells (McSCs) declines with age and that Brn2 promotes melanocyte stem cell regeneration by restraining stress-induced melanocytic differentiation. Our findings establish a previously unrecognized in vivo requirement for BRN2 in preserving the integrity of the melanocyte lineage following ionizing radiation, revealing a stress-dependent function distinct from its largely dispensable role in steady-state McSC maintenance.
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BibTeX
@misc{raymond2026brn2,
title = {{BRN2 preserves the melanocyte lineage following ionizing radiation}},
author = {J. 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 and L. Larue},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.18.759918},
url = {https://www.biorxiv.org/content/10.64898/2026.10.18.759918v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - BRN2 preserves the melanocyte lineage following ionizing radiation
AU - J. 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
AU - L. Larue
PY - 2026
DA - 2026/10/18
PB - bioRxiv
DO - 10.64898/2026.10.18.759918
UR - https://www.biorxiv.org/content/10.64898/2026.10.18.759918v1
AB - Adult stem cells maintain tissue homeostasis, but mechanisms preserving their integrity under stress remain incompletely understood. Here, we identify BRN2 (POU3F2), previously implicated in neuronal development, reprogramming of fibroblasts to neurons and in melanoma proliferation, migration and DNA-damage responses, as a key guardian of melanocyte stem cells. Remarkably, we reveal that while Brn2-deficient mice maintain their McSC compartment and normal pigmentation for up to 95 weeks, in contrast, rapid, dose-dependent, permanent hair depigmentation associated with the disappearance of detectable McSCs and differentiated melanocytes occurs in Brn2 KO mice exposed to ionizing radiation but not in WT mice. Importantly, our results indicate that in human follicular melanocytes BRN2 activity in melanocyte stem cells (McSCs) declines with age and that Brn2 promotes melanocyte stem cell regeneration by restraining stress-induced melanocytic differentiation. Our findings establish a previously unrecognized in vivo requirement for BRN2 in preserving the integrity of the melanocyte lineage following ionizing radiation, revealing a stress-dependent function distinct from its largely dispensable role in steady-state McSC maintenance.
ER -