Distinct migration patterns of adult neural stem cells derived from hippocampal and ventricular niches

Adult neurogenesis occurs in the two primary areas of the human brain, namely the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles. Neural stem cells (NSCs) from these niches generate new neurons and glia that contribute to plasticity and repair; however, their niche-associated cellular behaviors remain poorly characterized due to limited access to human brain tissue and the lack of physiologically relevant in vitro models. Here, we comparatively investigated the morphological features, migration behaviors, and neural-glia organization of NSCs derived from the SGZ and SVZ of the adult mouse brain using microfluidic-based cultures. SVZ-derived NSCs exhibited longer neurites, greater motility, and dispersed migration patterns, whereas SGZ-derived NSCs displayed shorter neurites, reduced motility, and collective, radial migration. In bilayer spheroid cultures, SGZ progenitors retained higher proportions of TUJ1⁺ and GFAP⁺ cells in the inner core over time, reflecting compact local integration characteristic of the dentate gyrus (DG), whereas SVZ progenitors dispersed outward, with fewer cells retained centrally, consistent with tangential migration along the rostral migratory stream. Exposure of DG-hippocampal spheroids to oligomeric amyloid-β (Aβ), followed by morphological assessments and targeted gene-expression profiling, showed disruption of spheroid organization along with enrichment of neuroinflammatory- and apoptosis-related gene signatures, suggesting that the model reflects selected features of Aβ-induced neurotoxicity. Together, these findings characterize niche-associated differences in the migration dynamics of adult NSCs in vitro and suggest an engineered platform for future mechanistic studies and disease modeling.