HOPX Defines Heterogeneity of Postnatal Subventricular Zone Neural Stem Cells

Abstract

Summary: The largest diversity of neural lineages generated from the subventricular zone (SVZ) occurs early after birth and is regulated in a spatiotemporal manner depending on the expression of specific transcriptional cues. Transcriptomics and fate-mapping approaches were employed to explore the relationship between regional expression of transcription factors by neural stem cells (NSCs) and the specification of distinct neural lineages. Our results support an early priming of NSCs for the genesis of defined cell types depending on their spatial location in the SVZ and identify HOPX as a marker of a subpopulation primed toward astrocytic fates. Manipulation of HOPX expression, however, showed no effect on astrogenesis but resulted in marked changes in the number of NSCs and of their progenies. Taken together, our results highlight transcriptional and spatial heterogeneity of postnatal NSCs and reveal a key role for HOPX in controlling SVZ germinal activity. : In this study, Zweifel et al. explore the early-lineage priming of NSCs of the postnatal SVZ. They identify HOPX as a marker of a dorsally located segregated subpopulation of NSCs primed towards astrocytic fates, thereby revealing novel regional heterogeneities of this germinal zone. Furthermore, Hopx overexpression results in marked changes in the number of NSCs and of their progenies. Keywords: subventricular zone, postnatal, gliogenesis, neurogenesis, transcriptional heterogeneity, regionalization, radial glia, outer radial glia