Single-cell transcriptomics characterizes cell types in the subventricular zone and uncovers molecular defects impairing adult neurogenesis

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Item Type:

Article

Title:

Single-cell transcriptomics characterizes cell types in the subventricular zone and uncovers molecular defects impairing adult neurogenesis

Creators Name:

Zywitza, V. and Misios, A. and Bunatyan, L. and Willnow, T.E. and Rajewsky, N.

Abstract:

Neural stem cells (NSCs) contribute to plasticity and repair of the adult brain. Niches harboring NSCs regulate stem cell self-renewal and differentiation. We used comprehensive and untargeted single-cell RNA profiling to generate a molecular cell atlas of the largest germinal region of the adult mouse brain, the subventricular zone (SVZ). We characterized >20 neural and non-neural cell types and gained insights into the dynamics of neurogenesis by predicting future cell states based on computational analysis of RNA kinetics. Furthermore, we applied our single-cell approach to document decreased numbers of NSCs, reduced proliferation activity of progenitors, and perturbations in Wnt and BMP signaling pathways in mice lacking LRP2, an endocytic receptor required for SVZ maintenance. Our data provide a valuable resource to study adult neurogenesis and a proof of principle for the power of single-cell RNA sequencing to elucidate neural cell-type-specific alterations in loss-of-function models.

Keywords:

Adult Neurogenesis, Neurogenic Niche, Subventricular Zone, Adult Neural Stem Cells, Single-Cell RNA Sequencing, Drop-Seq, LDL-Receptor Related Protein 2, RNA Velocity, Animals, Mice

Source:

Cell Reports

ISSN:

2211-1247

Publisher:

Cell Press / Elsevier

Volume:

Number:

Page Range:

2457-2469

Date:

27 November 2018