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

View ORCID ProfileVera Zywitza, Aristotelis Misios, Lena Bunatyan, View ORCID ProfileThomas E. Willnow, Nikolaus Rajewsky
doi: https://doi.org/10.1101/365619
Vera Zywitza
1Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Germany
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  • ORCID record for Vera Zywitza
Aristotelis Misios
1Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Germany
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Lena Bunatyan
2Molecular Cardiovascular Research, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Germany
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Thomas E. Willnow
2Molecular Cardiovascular Research, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Germany
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  • For correspondence: rajewsky@mdc-berlin.de willnow@mdc-berlin.de
Nikolaus Rajewsky
1Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Germany
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  • For correspondence: rajewsky@mdc-berlin.de willnow@mdc-berlin.de
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SUMMARY

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.

HIGHLIGHTS

  • unbiased single-cell transcriptomics characterizes adult NSCs and their niche

  • cell type-specific signatures and marker genes for 22 SVZ cell types

  • Free online tool to assess gene expression across 9,804 single cells

  • cell type-specific dysfunctions underlying impaired adult neurogenesis

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 09, 2018.
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Single-cell transcriptomics characterizes cell types in the subventricular zone and uncovers molecular defects underlying impaired adult neurogenesis
Vera Zywitza, Aristotelis Misios, Lena Bunatyan, Thomas E. Willnow, Nikolaus Rajewsky
bioRxiv 365619; doi: https://doi.org/10.1101/365619
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Single-cell transcriptomics characterizes cell types in the subventricular zone and uncovers molecular defects underlying impaired adult neurogenesis
Vera Zywitza, Aristotelis Misios, Lena Bunatyan, Thomas E. Willnow, Nikolaus Rajewsky
bioRxiv 365619; doi: https://doi.org/10.1101/365619

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