Identification of region-specific astrocyte subtypes at single cell resolution

TLDR

Astrocytes modulate synapse formation, synaptic transmission, blood–brain barrier formation, blood flow regulation, and metabolic support, with emerging evidence of region‑specific adaptations in the spinal cord and cerebellum. The study aims to map astrocyte molecular diversity across forebrain regions using single‑cell RNA sequencing. Single‑cell RNA sequencing of adult mouse cortex and hippocampus was performed to profile astrocyte transcriptomes. Analysis revealed five transcriptomically distinct astrocyte subtypes in adult mouse cortex and hippocampus, each with distinct spatial localization, demonstrating specialized regional astrocyte populations and providing an online database for further study.

Abstract

Abstract Astrocytes, a major cell type found throughout the central nervous system, have general roles in the modulation of synapse formation and synaptic transmission, blood–brain barrier formation, and regulation of blood flow, as well as metabolic support of other brain resident cells. Crucially, emerging evidence shows specific adaptations and astrocyte-encoded functions in regions, such as the spinal cord and cerebellum. To investigate the true extent of astrocyte molecular diversity across forebrain regions, we used single-cell RNA sequencing. Our analysis identifies five transcriptomically distinct astrocyte subtypes in adult mouse cortex and hippocampus. Validation of our data in situ reveals distinct spatial positioning of defined subtypes, reflecting the distribution of morphologically and physiologically distinct astrocyte populations. Our findings are evidence for specialized astrocyte subtypes between and within brain regions. The data are available through an online database ( https://holt-sc.glialab.org/ ), providing a resource on which to base explorations of local astrocyte diversity and function in the brain.