Neural Stem Cells in Adult Mammals are not Astrocytes

Abstract

At the turn of the 21st century studies of the cells that resided in the adult mammalian subventricular zone (SVZ) characterized the neural stem cells (NSCs) as a subtype of astrocyte. Over the ensuing years, numerous studies have further characterized the properties of these NSCs and compared them to parenchymal astrocytes. Here we have evaluated the evidence collected to date to establish whether classifying the NSCs as astrocytes is appropriate and useful. We also performed a meta-analysis with 4 previously published datasets that used cell sorting and unbiased single-cell RNAseq to highlight the distinct gene expression profiles of adult murine NSCs and niche astrocytes. On the basis of our understanding of the properties and functions of astrocytes versus the properties and functions of NSCs, and from our comparative transcriptomic analyses we conclude that classifying the adult mammalian NSC as an astrocyte is potentially misleading. From our vantage point, it is more appropriate to refer to the cells in the adult mammalian SVZ that retain the capacity to produce new neurons and macroglia as NSCs without attaching the term "astrocyte-like."

Keywords: Subventricular zone; adult; astrocytes; human; mouse; review; stem cells.

Figure 1.

(A) Venn diagram for DEGs between NSC and astrocyte populations from the three studies, Beckervordersandforth et al. (2010; blue), Dulken et al. (2017; yellow) and Zywitza et al. (2018; green). Each list represents a direct comparison in gene expression between NSCs and astrocytes in the reference study. (B) Circos plot for the same gene lists as (A), representing shared genes (shaded orange and purple lines) and shared GO terms (blue lines). GO enrichment analysis performed in Metascape.

Figure 2.

(A) Circos plot comparing full gene lists for NSCs (blue) and astrocytes (red) from Dulken et al. (2017). Shared genes are represented by shaded orange and purple lines. (B) Heatmap representing the association of GO terms (by p-value) and clusterization of GO terms between the same NSC and astrocyte populations as in (A). Astrocyte exclusive GO terms are highlighted in red. GO enrichment analysis performed in Metascape.

Figure 3.

Upset plot for the genes that characterize each of the five astrocyte populations identified by Mizrak et al. (2019). Blue bars represent the total number of genes in each group. Red columns represent the number of common genes defined by the corresponding relationship matrix (black connecting dots). Analysis performed in Intervene.