Astrocytes are glial cells that tile the nervous system and have complex morphology characterized by multiple branch levels and fine processes. Astrocytes have been regarded as largely identical until recently despite having a large degree of functional diversity. Batiuk et al (2020) explored the molecular diversity of astrocytes using single-cell RNA sequencing. Astrocytes were divided into 5 subtypes (AST1-5) based on the expression of 886 highly variable genes with AST5 being the least abundant (1.4%) and AST1 being the most abundant (36.5%). Furthermore, some subtypes are localized to specific brain regions as AST1 and AST4 are predominantly hippocampal while AST2 is mainly cortical. While some genes are expressed across all subtypes over 70% of enriched genes are specific to a subtype. AST4 was linked to neurogene sis as the enriched genes in this subtype show involvement in mitosis, cell cycle control, transcriptional regulation, neurogenesis, and neuronal differentiation. While AST5 showed considerable overlap with AST4, it was also enriched in genes coding for traditional astrocyte functions such as glucose metabolism. AST1-3 were grouped together as they all showed gene enrichment profiles indicating mature astrocyte function. AST1 showed a distinct specialization in synaptogenesis, synaptic plasticity, and glutamatergic neurotransmission. After establishing the molecular differences among astrocytes, Batiuk et al (2020) looked to explore morphological differences. They found smaller territorial volume in AST2 and 3 which are localized in cortical layers 2-4 when compared to AST3 which is localized to the hippocampal CA3 region. Going forward, it may be interesting to see more studies correlating the transcriptome to morphology and function as we learn more about region-specific astrocytes.
Saad
Reference
Batiuk, M.Y., Martirosyan, A., Wahis, J. et al. Identification of region-specific astrocyte subtypes at single cell resolution. Nat Commun 11, 1220 (2020).
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