Single-cell sequencing of the adult killifish (N. furzeri) brain identifies an atypical progenitor, glial and neuronal heterogeneity

Abstract

AbstractThe African turquoise killifish uniquely combines a short lifespan with vertebrate-specific features, including age-dependent loss of neuroregenerative capacity, that are missing from the currently used model organisms. In this study, we investigate the cellular landscape that shapes adult neuro- and gliogenesis using single-cell sequencing. Our analysis identifies seventeen cell types including neuronal cells (NC), and progenitors (PC) of glial and non-glial nature in the adult killifish telencephalon. PC subclustering unveils four radial glia types, one atypical non-glial progenitor (NGP) and two clusters representing transitioning states. NC subclustering classified neurons into immature and mature excitatory or inhibitory sub-clusters. Using lineage inference analysis, we discovered neuroepithelial-like radial glia to be the source of neuro- and gliogenesis, and a central role for NGP. Our findings are evidence for specialized progenitors within telencephalon and the data is accessible via an online database, providing a resource to understand normal brain function, as well as the role of cellular relationships in response to injury and disease.HighlightsSingle-cell transcriptomics reveals four radial glial and one non-glial progenitor cell types relevant to the neurogenic potential of the adult killifish telencephalonIterative clustering of neuronal cell types identified two immature and multiple mature neuron subclassesLineage inference analysis of progenitor cell types suggests a neuroepithelial-like radial glia population as the start point of neuro- and gliogenesis, that generates the proliferative non-glial progenitorKillifish-specific marker genes are identified for all the telencephalic cell types, with a special emphasis on markers for the non-glial progenitor, neuron subclasses and radial glia sub-types