PER2- and state-dependent transcriptional programs gate neural stem cell proliferation with niche-specific circadian autonomy
- 1IMBA - Institute of Molecular Biotechnology of Austria
Abstract
Adult neural stem cells (NSCs) in the mouse brain are predominantly quiescent, with activation tightly regulated to balance neurogenesis and stem cell maintenance. Circadian clocks temporally organize core cellular processes, potentially gating NSC activation. We examined adult NSC temporal dynamics across the day and observed rhythmic expression of core circadian clock components BMAL1 and PER2 in both mammalian niches, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ). While cell cultures derived from both niches show BMAL1 and PER2 protein, only SGZ-derived NSCs exhibit synchronized self-sustained core clock oscillations across the population. Comparative analyses of WT and Per2 knockout NSCs revealed state-specific, circadian clock-dependent oscillatory transcriptional programs. This identified ASCL1 and CCND1 as candidate regulators of cell-cycle coordination, with daytime accumulation preceding a nighttime S-phase peak. The temporal control of S-phase entry in NSCs was abolished in Per2 knockout mice. Together, our findings reveal state-specific, PER2-dependent circadian regulation of adult NSCs in both neurogenic niches, and a specific dependence on external stimuli for synchronization in the SVZ.
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BibTeX
@misc{brum2026per2,
title = {{PER2- and state-dependent transcriptional programs gate neural stem cell proliferation with niche-specific circadian autonomy}},
author = {P. O. Brum and A. Abdi and F. Scaramuzza and T. Kepcija and M. H. Hastings and A. S. I. Loudon and K. Tessmar-Raible and N. Urban Avellaneda},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.751519},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751519v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - PER2- and state-dependent transcriptional programs gate neural stem cell proliferation with niche-specific circadian autonomy
AU - P. O. Brum
AU - A. Abdi
AU - F. Scaramuzza
AU - T. Kepcija
AU - M. H. Hastings
AU - A. S. I. Loudon
AU - K. Tessmar-Raible
AU - N. Urban Avellaneda
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.751519
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.751519v1
AB - Adult neural stem cells (NSCs) in the mouse brain are predominantly quiescent, with activation tightly regulated to balance neurogenesis and stem cell maintenance. Circadian clocks temporally organize core cellular processes, potentially gating NSC activation. We examined adult NSC temporal dynamics across the day and observed rhythmic expression of core circadian clock components BMAL1 and PER2 in both mammalian niches, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ). While cell cultures derived from both niches show BMAL1 and PER2 protein, only SGZ-derived NSCs exhibit synchronized self-sustained core clock oscillations across the population. Comparative analyses of WT and Per2 knockout NSCs revealed state-specific, circadian clock-dependent oscillatory transcriptional programs. This identified ASCL1 and CCND1 as candidate regulators of cell-cycle coordination, with daytime accumulation preceding a nighttime S-phase peak. The temporal control of S-phase entry in NSCs was abolished in Per2 knockout mice. Together, our findings reveal state-specific, PER2-dependent circadian regulation of adult NSCs in both neurogenic niches, and a specific dependence on external stimuli for synchronization in the SVZ.
ER -