Single-cell analysis of the ventricular-subventricular zone reveals signatures of dorsal & ventral adult neurogenesis
- University of California, San Francisco, United States
- Instituto Cavanilles, Universidad de Valencia, y Unidad Mixta de Esclerosis Múltiple y Neurorregeneración, CIBERNED, Spain
Abstract
The ventricular-subventricular zone (V-SVZ), on the walls of the lateral ventricles, harbors the layrgest neurogenic niche in the adult mouse brain. Previous work has shown that neural steym/progenitor cells (NSPCs) in different locations within the V-SVZ produce different subtypes of new neurons for the olfactory bulb. The molecular signatures that underlie this regional heterogeneity remain largely unknown. Here we present a single-cell RNA-sequencing dataset of the adult mouse V-SVZ revealing two populations of NSPCs that reside in largely non-overlapping domains in either the dorsal or ventral V-SVZ. These regional differences in gene expression were further validated using a single-nucleus RNA-sequencing reference dataset of regionally microdissected domains of the V-SVZ and by immunocytochemistry and RNAscope localization. We also identify two subpopulations of young neurons that have gene expression profiles consistent with a dorsal or ventral origin. Interestingly, a subset of genes are dynamically expressed, but maintained, in the ventral or dorsal lineages. The study provides novel markers and territories to understand the region-specific regulation of adult neurogenesis.
Data availability
The RNA sequencing datasets generated for this manuscript are deposited in the following locations: scRNA-Seq and sNucRNA-Seq GEO Data Series: GSE165555.Processed data (CellRanger output .mtx and .tsv files, and Seurat Object .rds files) are available as supplementary files within the scRNA-Seq (GSE165554) or sNucRNA-Seq (GSE165551) data series or individual sample entries listed within each data series.Web-based, interactive versions of the scRNA-Seq and sNucRNA-Seq datasets are available from the University of California Santa Cruz Cell Browser: https://svzneurogeniclineage.cells.ucsc.eduThe code used to analyze the datasets and generate the figures are available at the following location: https://github.com/AlvarezBuyllaLab?tab=repositories
Article and author information
Author details
Arturo Álvarez-Buylla
Funding
Generalitat Valenciana (APOSTD2018/A113)
- Arantxa Cebrian Silla
University of California, San Francisco (John G. Bowes Research Fund and the UCSF PBBR partially funded by the Sandler Foundation)
- Arturo Álvarez-Buylla
National Institutes of Health (R01 NS112357)
- Arturo Álvarez-Buylla
National Institutes of Health (F32 (NS103221))
- Stephanie A Redmond
National Institutes of Health (K99 (NS121273))
- Stephanie A Redmond
National Institutes of Health (F31 NS106868)
- David Wu
National Institutes of Health (R37 HD032116)
- Arturo Álvarez-Buylla
National Institutes of Health (R01 NS028478)
- Arturo Álvarez-Buylla
National Institutes of Health (R01 NS113910)
- Arturo Álvarez-Buylla
National Institutes of Health (R01 NS091544)
- Daniel Lim
U.S. Department of Veterans Affairs (1I01 BX000252)
- Daniel Lim
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Mice were housed on a 12h day-night cycle with free access to water and food in a specific pathogen-free facility in social cages (up to 5 mice/cage) and treated according to the guidelines from the UCSF. Institutional Animal Care and Use Committee (IACUC) and NIH. All mice used in this study were healthy and immuno-competent, and did not undergo previous procedures unrelated to the experiment. CD1-elite mice (Charles River Laboratories) and hGFAP::GFP (FVB/N-Tg(GFAPGFP)14Mes/J, The Jackson Laboratory (003257)) (Zhuo et al., 1997) lines were used. Sample sizes were chosen to generate sufficient numbers of high-quality single cells for RNA sequencing, including variables such as sex, and identifying potential batch effects. Biological and technical replicates for each experiment are described in the relevant subsections below.
Copyright
© 2021, Cebrian Silla et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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