Transcriptional heterogeneity of ventricular zone cells throughout the embryonic mouse forebrain

Abstract

The ventricular zone (VZ) of the nervous system contains radial glia cells that were originally considered relatively homogenous in their gene expression. However, a detailed characterization of transcriptional diversity in these VZ cells has not been reported. Here, we performed single-cell RNA sequencing to characterize transcriptional heterogeneity of neural progenitors within the VZ and subventricular zone (SVZ) of the mouse embryonic cortex and ganglionic eminences (GEs). By using a transgenic mouse line to enrich for VZ cells, we detect significant transcriptional heterogeneity within VZ and SVZ progenitors, both between forebrain regions and within spatial subdomains of specific GEs. Additionally, we observe differential gene expression between E12.5 and E14.5 VZ cells, which could provide insights into temporal changes in cell fate. Together, our results reveal a previously unknown spatial and temporal genetic diversity of telencephalic VZ cells that will aid our understanding of initial fate decisions in the forebrain.

Loss of Ezh2 in the medial ganglionic eminence alters interneuron fate, cell morphology and gene expression profiles

“…Several factors regulate initial interneuron fate decisions within the MGE, including gradients of diffusible cues, spatial location of progenitors, temporal birthdates and the mode of neurogenesis (Flames et al, 2007;Glickstein et al, 2007;Wonders et al, 2008;Inan et al, 2012;Petros et al, 2015;Bandler et al, 2017Bandler et al, , 2021Mi et al, 2018;Allaway et al, 2021). The advent of single cell sequencing technologies over the last decade has generated a transcriptional and epigenetic 'ground truth' in the ganglionic eminences in mice (Mayer et al, 2018;Mi et al, 2018;Allaway et al, 2021;Bandler et al, 2021;Lee et al, 2022a;Rhodes et al, 2022), and more recently, in primates and humans (Nowakowski et al, 2017;Eze et al, 2021;Shi et al, 2021;Yu et al, 2021;Braun et al, 2022;Schmitz et al, 2022;Velmeshev et al, 2022;Zhao et al, 2022). With this baseline in place, researchers can better characterize how genetic and epigenetic perturbations affect the fate and maturation of GABAergic interneurons.…”