Dissecting the spatiotemporal diversity of adult neural stem cells

Adult stem cells are important for tissue turnover and regeneration. However, in most adult systems it remains elusive how stem cells assume different functional states and support spatially patterned tissue architecture. Here, we dissected the diversity of neural stem cells in the adult zebrafish brain, an organ that is characterized by pronounced zonation and high regenerative capacity. We combined single-cell transcriptomics of dissected brain regions with massively parallel lineage tracing and in vivo RNA metabolic labeling to analyze the regulation of neural stem cells in space and time. We detected a large diversity of neural stem cells, with some subtypes being restricted to a single brain region, while others were found globally across the brain. Global stem cell states are linked to neurogenic differentiation, with different states being involved in proliferative and non-proliferative differentiation. Our work reveals principles of adult stem cell organization and establishes a resource for the functional manipulation of neural stem cell subtypes. Single-cell transcriptomics, massively parallel lineage tracing and in vivo RNA metabolic labeling are used to dissect the diversity of neural stem cells in the adult zebrafish brain, an organ characterized by pronounced zonation and high regenerative capacity.A diversity of radial glia states is detected in the adult zebrafish brain, with some states being regional and others global across the brain. Global radial glia states tend to be linked to neurogenic differentiation, while regional radial glia states appear to predominantly have tissue maintenance function. Proliferative and non-proliferative differentiation proceed along separate trajectories and involve different radial glia states. Cell state transitions and differentiation trajectories are validated by single-cell RNA metabolic labeling. Single-cell transcriptomics, massively parallel lineage tracing and in vivo RNA metabolic labeling are used to dissect the diversity of neural stem cells in the adult zebrafish brain, an organ characterized by pronounced zonation and high regenerative capacity.