CRISPR-mediated activation of endogenous Fabp7 enhances regenerative capacity of aged neural stem/progenitor cells

Neural stem/progenitor cells (NSPCs) are multipotent cells in the central nervous system (CNS) that give rise to specialized neuronal and glial cells. With age, the number and activity of NSPCs decline significantly, leading to reduced proliferation, differentiation, and survival of newborn neurons. Beyond their role in generating new cells, NSPCs secrete a complex mixture of signaling molecules—including growth factors, cytokines, metabolites, and lipids—that contribute to cellular rejuvenation and tissue repair. However, the specific physiological roles of these secreted factors and their contribution to age-related decline remain unclear. Here, we investigate the secretome of early postnatal NSPCs and identify Fatty Acid Binding Protein 7 (Fabp7) as a candidate rejuvenation factor. To overcome the technical challenges of studying a single secreted molecule in vivo, we developed an NSPC-specific CRISPR/Cas9-mediated activation system. Our findings demonstrate that Fabp7 plays an important role in maintaining NSPC stemness and that its targeted activation can counteract age-related neurogenic decline.