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Cell Rep. 2018 Nov 27;25(9):2457-2469.e8. doi: 10.1016/j.celrep.2018.11.003.

Single-Cell Transcriptomics Characterizes Cell Types in the Subventricular Zone and Uncovers Molecular Defects Impairing Adult Neurogenesis.

Author information

1
Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13092 Berlin-Buch, Germany.
2
Molecular Cardiovascular Research, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13092 Berlin-Buch, Germany.
3
Molecular Cardiovascular Research, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13092 Berlin-Buch, Germany. Electronic address: willnow@mdc-berlin.de.
4
Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13092 Berlin-Buch, Germany. Electronic address: rajewsky@mdc-berlin.de.

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:

Drop-seq; LDL-receptor related protein 2; RNA velocity; adult neural stem cells; adult neurogenesis; neurogenic niche; single-cell RNA sequencing; subventricular zone

PMID:
30485812
DOI:
10.1016/j.celrep.2018.11.003
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