Single cell transcriptomic analysis defines heterogeneity and transcriptional dynamics in the adult neural stem cell lineage

Summary

Neural stem cells (NSCs) in the adult mammalian brain serve as a reservoir for the generation of new neurons, oligodendrocytes, and astrocytes. Here we use single cell RNA-sequencing to characterize adult NSC populations and examine the molecular identities and heterogeneity of in vivo NSC populations. We find that cells in the NSC lineage exist on a continuum through the processes of activation and differentiation. Interestingly, rare intermediate states with distinct molecular profiles can be identified and experimentally validated, and our analysis identifies putative surface markers and key intracellular regulators for these subpopulations of NSCs. Finally, using the power of single cell profiling, we conduct a meta-analysis to compare in vivo NSCs and in vitro cultures, distinct fluorescent-activated cell sorting strategies, and different neurogenic niches. These data provide a resource for the field and contribute to an integrative understanding of the adult NSC lineage.

ETOC Blurb

Dulken et al. perform single cell transcriptomics on neural stem cells (NSCs) from adult mice. They use machine learning to identify rare intermediate cells in the continuum of the NSC lineage and perform a meta-analysis with other single cell transcriptomic data from in vitro or in vivo NSCs.