Numerical data supporting figures.

Quiescent neural stem cells (qNSCs) in the adult mouse subventricular zone (SVZ) normally have limited capacity to generate glia. Gliogenic domains are present in both dorsal and ventral SVZ, with the ventral region featuring a subpopulation of Gli1+ qNSCs. In dorsal SVZ, however, the molecular identity and developmental origin of oligodendrogenic qNSCs remains elusive. Here, through single-cell analysis and lineage tracing, we identify an undefined subpopulation of Gas1high qNSCs in dorsal SVZ, distinct from Gli1+ qNSCs. These cells originate from embryonic Gas1high dorsal radial glia, and persist into the aged SVZ. Remarkably, they are multipotent and more gliogenic than Gas1low/− qNSCs, continuously generating oligodendrocytes in the adult and aged brain, and can be mobilized for myelin repair upon demyelination. Together, our study uncovers a subpopulation of dorsally derived, multipotent long-term qNSCs in the adult and aged SVZ with enhanced gliogenic potential, shedding light on the heterogeneity and plasticity of NSCs in normal, aging, and disease conditions.

成年小鼠脑室下区（subventricular zone, SVZ）的静息态神经干细胞（quiescent neural stem cells, qNSCs）通常仅具备有限的胶质细胞生成能力。背侧与腹侧SVZ均存在生胶质域，其中腹侧区域存在一群Gli1阳性的qNSCs亚群。然而，背侧SVZ内负责生成少突胶质细胞的qNSCs的分子特征与发育起源仍不明确。本研究通过单细胞分析与谱系示踪技术，在背侧SVZ中鉴定出一群此前未被表征的Gas1高表达qNSCs亚群，该亚群与Gli1阳性qNSCs存在显著区别。这群细胞起源于胚胎期Gas1高表达的背侧放射状胶质细胞，并可存续至衰老阶段的SVZ中。值得注意的是，该细胞亚群具备多向分化潜能，其生胶质能力强于Gas1低表达/阴性的qNSCs，可在成年及衰老大脑中持续生成少突胶质细胞，且在脱髓鞘损伤时可被激活以参与髓鞘修复。综上，本研究揭示了成年及衰老SVZ中一群背侧起源、具备长期存活特性且生胶质潜能增强的多能qNSCs亚群，为阐明神经干细胞在正常生理、衰老及疾病状态下的异质性与可塑性提供了新的研究思路。