Dataset Information

Identification of a Subpopulation of Astrocyte Progenitor Cells in the Neonatal Subventricular Zone: Evidence that Migration is Regulated by Glutamate Signaling

ABSTRACT: In adult mice engineered to express enhanced green fluorescent protein (eGFP) under the control of the glutamate transporter 1 (GLT1) gene, eGFP is found in all cortical astrocytes. However, when 8.3 kilobases of the human GLT1/EAAT2 gene is used to control expression of tdTomato (tdT), tdT is only found in a subpopulation of cortical astrocytes. The eGFP mice have been used to define mechanisms of transcriptional regulation using astrocytes cultured from cortex of 1-3 day old mice. Using the same cultures, we were never able to induce tdT+ expression. We hypothesized that these cells might not have migrated into the cortex by this age. In this study, we characterized the ontogeny of tdT+ cells, performed single-cell RNA sequencing (scRNA-seq), and tracked their migration in organotypic slice cultures. At postnatal day (PND) 1, tdT+ cells were observed in the subventricular zone and striatum but not in the cortex, and they did not express eGFP. At PND7, tdT+ cells began to appear in the cortex with their numbers increasing with age. At PND1, scRNA-seq demonstrates that the tdT+ cells are molecularly heterogeneous, with a subpopulation expressing astrocytic markers, subsequently validated with immunofluorescence. In organotypic slices, tdT+ cells migrate into the cortex and express GLT1, NF1A, and eGFP after 7 days. Ionotropic glutamate receptor (iGluR) antagonists reduced (25 to 50%) the distance tdT+ cells migrate from the subventricular zone into cortex. The pan-glutamate transport inhibitor, TFB-TBOA, dramatically increased (10-fold) the number of tdT+ cells in the cortex. In conclusion, although tdT is expressed by non-glial cells at PND1, it is also expressed by glial progenitors that migrate into the cortex postnatally. With this fluorescent labelling, we provide novel evidence that glutamate signaling contributes to the control of glia precursor migration.

ORGANISM(S): Mus musculus

PROVIDER: GSE273223 | GEO | 2025/01/15

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:We sought to characterize cellular heterogeneity in the human cerebral cortex at a molecular level during cortical neurogenesis. We captured single cells and generated sequencing libraries using the C1TM Single-Cell Auto Prep System (Fluidigm), the SMARTer Ultra Low RNA Kit (Clontech), and the Nextera XT DNA Sample Preparation Kit (Illumina). We performed unbiased clustering of the single cells and further examined transcriptional variation among cell groups interpreted as radial glia. Within this population, the major sources of variation related to cell cycle progression and the stem cell niche from which radial glia were captured. We found that outer subventricular zone radial glia (oRG cells) preferentially express genes related to extracellular matrix formation, migration, and stemness, including TNC, PTPRZ1, FAM107A, HOPX, and LIFR and related this transcriptional state to the position, morphology, and cell behaviors previously used to classify the cell type. Our results suggest that oRG cells maintain the subventricular niche through local production of growth factors, potentiation of growth factor signals by extracellular matrix proteins, and activation of self-renewal pathways, thereby contributing to the developmental and evolutionary expansion of the human neocortex. For study version 2, we have updated this data set to include additional primary cells that we infer to represent microglia, endothelial cells, and immature astrocytes, as well as additional cells from the developing neural retina, and from iPS-cell derived cerebral organoids. The genes distinguishing these cell populations may reveal biological processes supporting the diverse functions of these cell types as well as vulnerabilities of specific cell types in human genetic diseases and in viral infections. For study version 3, we have updated the data set to include additional primary cells, including those published in Nowakowski, et al., Science 2017: "Spatiotemporal Gene Expression Trajectories Reveal Developmental Hierarchies of the Human Cortex" (in press)

Dataset Information

Identification of a Subpopulation of Astrocyte Progenitor Cells in the Neonatal Subventricular Zone: Evidence that Migration is Regulated by Glutamate Signaling

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets