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

Item Type:

Preprint

Title:

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 are crucial for regulating stem cell self-renewal and differentiation. We used single-cell RNA profiling to generate an unbiased molecular atlas of all cell types in the largest neurogenic niche 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 apply our single-cell approach to mice lacking LRP2, an endocytic receptor required for SVZ maintenance. The number of NSCs and proliferating progenitors was significantly reduced. Moreover, Wnt and BMP4 signaling was perturbed. We provide a valuable resource for adult neurogenesis, insights into SVZ neurogenesis regulation by LRP2, and a proof-of-principle demonstrating the power of single-cell RNA-seq in pinpointing neural cell type-specific functions in loss-of-function models.

Keywords:

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

Source:

bioRxiv

Publisher:

Cold Spring Harbor Laboratory Press

Article Number:

365619

Date:

9 July 2018

Official Publication:

https://doi.org/10.1101/365619

Related to:

URL	URL Type
http://edoc.mdc-berlin.de/17904/	Final version

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