The sequences for sgRNA and PCR primers.

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）内的静息神经干细胞（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均存在胶质生成域，其中腹侧区域特有一群Gli1阳性的qNSCs亚群。然而，背侧SVZ中负责少突胶质细胞生成的qNSCs的分子标识与发育起源仍未明确。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界定的Gas1高表达qNSCs亚群，该亚群与Gli1阳性qNSCs截然不同。这类细胞起源于胚胎期Gas1高表达的背侧放射状胶质细胞，并可存续至衰老状态的SVZ中。值得注意的是，该亚群具备多能分化潜能，且相较于Gas1低表达/阴性的qNSCs具有更强的胶质生成能力，可在成年及衰老大脑中持续产生少突胶质细胞；在脱髓鞘损伤后，这类细胞还可被动员以参与髓鞘修复。综上，本研究揭示了成年及衰老SVZ中一群背侧起源、可长期存续且胶质生成潜能增强的多能qNSCs亚群，为阐明正常生理、衰老及疾病状态下神经干细胞的异质性与可塑性提供了新的理论依据。