Single cell sequencing unravels the cellular diversity that shapes neuro- and gliogenesis in the fast aging killifish (N. furzeri) brain

The African turquoise killifish combines a short lifespan with age-dependent loss of neuroregenerative capacity, making it a well-suited model for studying brain repair mechanisms in the context of aging. To investigate the extent of cellular diversity that shapes neuro- and gliogenesis, we performed single cell sequencing of the adult telencephalon. Our analysis identifies seventeen cell types including neuronal cells, and progenitors of glial and non-glial nature. Further subclustering unveils four radial glia (RG) types, one atypical non-glial progenitor (NGP) and two intermediate subtypes. Validation of our data in situ reveals a distinct spatial setting for defined RG subtypes, reflecting the distribution of morphologically and physiologically distinct populations. Lineage inference analysis suggests neuroepithelial-like radial glia and NGP to be the start point and intercessor of neural development, respectively. Neuronal sub-clustering uncovers immature and mature excitatory or inhibitory sub-clusters. This complete catalogue of killifish telencephalon cell types is accessible via an online tool, providing a resource to understand neurogenesis in healthy brains and upon injury or disease. Telencephalon region (homologous to mammalian SGZ/SVZ) of the 6-week-old adult female killifish was harvested for single-cell RNA sequencing.