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

Zywitza, Vera; Misios, Aristotelis; Bunatyan, Lena; Willnow, Thomas E.; Rajewsky, Nikolaus

doi:10.1016/j.celrep.2018.11.003

Cited by 156 publications

(191 citation statements)

References 61 publications

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“…Here, we show that constitutive or brain-specific deletion of GemC1 results in the development of severe congenital hydrocephalus in mice. We show that lack of GemC1 expression impedes early commitment of showing the number of genes displaying increased or decreased promoter accessibility from GemC1-knockout cells that overlap signature genes for neural stem cells (data from Zywitza, Misios, Bunatyan, Willnow, & Rajewsky, 2018 (Mizrak et al, 2019). A higher number of Ki67+ and DCX-expressing cells was identified in the medial wall of GemC1 cKO brains, suggesting that neurogenesis is positively regulated in the absence of GemC1.…”

Section: Discussionmentioning

confidence: 79%

“…(D) Bar graphs showing the top most enriched GO terms/pathways for genes that display increased or decreased promoter accessibility. (E) Venn diagram (left) showing the number of genes displaying increased or decreased promoter accessibility from GemC1 ‐knockout cells that overlap signature genes for neural stem cells (data from Zywitza, Misios, Bunatyan, Willnow, & Rajewsky, ). Bar graph (right) shows the top most enriched GO terms/pathways for the highlighted (grey) gene subset in the Venn diagram [Color figure can be viewed at wileyonlinelibrary.com]…”

Section: Resultsmentioning

confidence: 99%

“…We compared genes exhibiting differential accessibility with signature genes of NSCs from the mouse SVZ (derived from single‐cell RNA‐seq data; Zywitza et al, ). Strikingly, 1/3 of these signature genes (listed in Supporting Information Table S1) could be seen “opening up” upon GemC1 KO/KO and concerned genes with functions relevant to neural system development and glial cell proliferation (Figure E).…”

Section: Resultsmentioning

confidence: 99%

“…We compared genes exhibiting differential accessibility with signature genes of NSCs from the mouse SVZ (derived from single-cell RNAseq data; Zywitza et al, 2018). Strikingly, 1/3 of these signature genes (listed in Supporting Information Table S1) could be seen "opening up"…”

Section: Ablation Of Gemc1 Induces Widespread Chromatin Accessibilimentioning

confidence: 99%

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GemC1 is a critical switch for neural stem cell generation in the postnatal brain

Lalioti

Kaplani

Lokka

et al. 2019

Glia

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The subventricular zone (SVZ) is one of two main niches where neurogenesis persists during adulthood, as it retains neural stem cells (NSCs) with self‐renewal capacity and multi‐lineage potency. Another critical cellular component of the niche is the population of postmitotic multiciliated ependymal cells. Both cell types are derived from radial glial cells that become specified to each lineage during embryogenesis. We show here that GemC1, encoding Geminin coiled‐coil domain‐containing protein 1, is associated with congenital hydrocephalus in humans and mice. Our results show that GemC1 deficiency drives cells toward a NSC phenotype, at the expense of multiciliated ependymal cell generation. The increased number of NSCs is accompanied by increased levels of proliferation and neurogenesis in the postnatal SVZ. Finally, GemC1‐knockout cells display altered chromatin organization at multiple loci, further supporting a NSC identity. Together, these findings suggest that GemC1 regulates the balance between NSC generation and ependymal cell differentiation, with implications for the pathogenesis of human congenital hydrocephalus.

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Section: Discussionmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Ablation Of Gemc1 Induces Widespread Chromatin Accessibilimentioning

confidence: 99%

See 2 more Smart Citations

GemC1 is a critical switch for neural stem cell generation in the postnatal brain

Lalioti

Kaplani

Lokka

et al. 2019

Glia

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show abstract

“…Comparing the molecule counts versus cells table from Eng et al . with single‐cell RNA‐sequencing data from the same regions of mouse brain, the data are highly comparable. While the scRNA‐seq data measures about twice as many genes across the datasets, the total molecule count per cell and the number of genes observed in an individual cell are almost the same.…”

mentioning

confidence: 83%

A method for transcriptome‐wide gene expression quantification in intact tissues

Svensson

2019

Immunol Cell Biol

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Single‐cell profiling for advancing birth defects research and prevention

Knudsen

Spielmann

Megason

et al. 2021

Birth Defects Research

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Cellular analysis of developmental processes and toxicities has traditionally entailed bulk methods (e.g., transcriptomics) that lack single cell resolution or tissue localization methods (e.g., immunostaining) that allow only a few genes to be monitored in each experiment. Recent technological advances have enabled interrogation of genomic function at the single-cell level, providing new opportunities to unravel developmental pathways and processes with unprecedented resolution. Here, we review emerging technologies of singlecell RNA-sequencing (scRNA-seq) to globally characterize the gene expression sets of different cell types and how different cell types emerge from earlier cell states in development. Cell atlases of experimental embryology and human embryogenesis at single-cell resolution will provide an encyclopedia of genes that define key stages from gastrulation to organogenesis. This technology, combined with computational models to discover key organizational principles, was recognized by Science magazine as the "Breakthrough of the year" for 2018 due to transformative potential on the way we study how human cells mature over a lifetime, how tissues regenerate, and how cells change in diseases (e.g., patient-derived organoids to screen disease-specific targets and design precision therapy). Profiling transcriptomes at the single-cell level can fulfill the need for greater detail in the molecular progression of all cell lineages, from pluripotency to adulthood and how cell-cell signaling pathways control progression at every step. Translational opportunities emerge for elucidating pathogenesis of genetic birth defects with cellular precision and improvements for predictive toxicology of chemical teratogenesis.

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

Cited by 156 publications

References 61 publications

GemC1 is a critical switch for neural stem cell generation in the postnatal brain

GemC1 is a critical switch for neural stem cell generation in the postnatal brain

A method for transcriptome‐wide gene expression quantification in intact tissues

Single‐cell profiling for advancing birth defects research and prevention

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