Single-Cell Transcriptomic Analysis Defines Heterogeneity and Transcriptional Dynamics in the Adult Neural Stem Cell Lineage

Cell Rep. 2017 Jan 17;18(3):777-790. doi: 10.1016/j.celrep.2016.12.060.

Abstract

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 fluorescence-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.

Keywords: adult neurogenesis; machine learning; neural stem cells; pseudotemporal ordering; single-cell RNA-seq.

MeSH terms

  • Algorithms
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Connexin 43 / genetics
  • Connexin 43 / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Ki-67 Antigen / metabolism
  • Mice
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurogenesis
  • Principal Component Analysis
  • RNA / chemistry
  • RNA / genetics
  • RNA / metabolism
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptome*

Substances

  • Connexin 43
  • Distal-less homeobox proteins
  • GJA1 protein, mouse
  • Homeodomain Proteins
  • Ki-67 Antigen
  • Transcription Factors
  • RNA
  • Atp1a2 protein, mouse
  • Sodium-Potassium-Exchanging ATPase