DEK facilitates regeneration in Stroke-Injured and Aging Brain via triggering Quiescence Exit of Neural Stem Cell

Quiescent neural stem cells (NSCs) in the adult mammalian brain can, upon activation, generate neurons and glial cells that contribute to complex sensory and cognitive functions during damage repair or aging. However, the specific and sustainable determinants of quiescent NSC activation remain unclear. Here, we present DEK as the primary activator of NSC quiescence in mice, functioning via the inhibition of downstream Notch signaling pathway. Overexpression of DEK in adult NSCs triggers quiescence exit, facilitating neurogenesis, eventually leading to either the rejuvenation of aged brains or the improved damage repair in a stroke-injured model. Meanwhile, persistent DEK overexpression from embryonic stages deprives NSCs of the ability to enter quiescence, leading to the ultimate depletion of the adult NSC reservoir, causing atrophy of hippocampus and deficits in spatial learning. Our findings establish a new narrative for quiescence exit of NSCs by DEK, potentially applicable when treating neurodegenerative diseases and brain injury. We performed gene expression profiling analysis using data obtained from RNA-seq of subventricular zone neural stem cells with AAV9-GFAP-GFP (Control) or AAV9-GFAP-DEK-GFP (DEK cOE) infection.