Developmental emergence of adult neural stem cells as revealed by single cell transcriptional profiling

Adult neural stem cells (NSCs) derive from embryonic precursors, but little is known about how or when this occurs. We have addressed this issue using single cell RNAseq at multiple developmental timepoints to analyze the embryonic murine cortex, one source of adult forebrain NSCs. We computationally identify all major cortical cell types, including the embryonic radial precursors (RPs) that generate adult NSCs. We define the initial emergence of RPs from neuroepithelial stem cells at E11.5. We show that by E13.5 these RPs express a transcriptional identity that is maintained and reinforced throughout their transition to a non-proliferative state between E15.5 and E17.5. These slowly-proliferating late embryonic RPs share a core transcriptional phenotype with quiescent adult forebrain NSCs. Together, these findings support a model where cortical RPs maintain a core transcriptional identity from embryogenesis through to adulthood, and where the transition to a quiescent adult NSC occurs during late neurogenesis. Overall design: We applied the high-throughput single-cell mRNA sequencing technique, Drop-seq, to the embryonic mouse cortex. 2000-5000 single cells from wildtype CD1 embryos of gestational ages E11.5, E13.5, E15.5 and E17.5 were characterized.

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Yuzwa SA, Borrett MJ, Innes BT, Voronova A, Ketela T, Kaplan DR, Bader GD, Miller FD