![]() ![]() Refined labeling strategies using promoter fragments 13, or intersectional approaches 14, 15 to isolate subpopulations of cells have revealed intra-regional heterogeneity in the cortex 13, 14, 15, as well as the brainstem, thalamus, olfactory bulb, cerebellum and spinal cord 14, which again correlates to morphology 15, cell intrinsic physiology 15 and function 13, 14.Īstrocytes are also involved in disease, as evidenced by extensive cell culture and mouse model studies 6, with disruption of astrocyte functions, such as synapse formation, leading to neuronal network dysfunction 13, 14. In addition, astrocytes in different brain regions also have distinct morphological and functional features, such as degree of synapse association 9, 10, intrinsic membrane properties and Ca 2+ signaling 10, and ability to promote neuronal maturation 12. Together, these studies revealed that gene expression varies between brain regions, and that there is often a subtle gradient of gene expression within individual brain areas. Fusion of reporter tags to ribosomal subunits (TRAP technology) has permitted the isolation of actively translated mRNAs from astrocytes 10, 11, 12. The expression of fluorescent reporter tags in astrocytes has allowed the isolation of cells from specific brain regions for RNA profiling 8, 9 and proteomic studies 10. However, the issue of astrocyte diversity is now being addressed and a number of studies are reporting heterogeneity of form and function, both between and within brain regions (see reviews by Khakh and Sofroniew 6, Ben Haim and Rowitch 7, Khakh and Deneen 3 and references therein). This is in contrast to studies on neurons, for which numerous experimental tools exist and evidence for substantial diversity within brain regions has accumulated 4, 5. The question of whether specialized astrocyte subtypes exist remains poorly resolved, largely due to the lack of experimental tools allowing detailed astrocyte characterization 3. Since then, our understanding of the molecular and cellular heterogeneity of astrocytes has remained largely unaltered: astrocyte classification has largely been restricted to two morphological groupings, fibrous and protoplasmic astrocytes, found in the white and gray matter of the brain, respectively. Extensive morphological heterogeneity of astrocyte populations was described over 100 years ago in seminal work by Ramón y Cajal 2. This degree of functional diversity begs the question of whether astrocytes are a homogeneous group of cells or exist in distinct subtypes with specialized functions. Paralleling the wide diversity of their interactions, astrocytes have been reported to play key roles in supporting CNS structure, metabolism, blood–brain barrier formation, and control of vascular blood flow, axon guidance, synapse formation, and modulation of synaptic transmission 1. They possess thousands of individual processes, which extend out into the neuropil, interacting with neurons, other glia, and blood vessels. The data are available through an online database ( ), providing a resource on which to base explorations of local astrocyte diversity and function in the brain.Īstrocytes are ubiquitous in the central nervous system (CNS). Our findings are evidence for specialized astrocyte subtypes between and within brain regions. Validation of our data in situ reveals distinct spatial positioning of defined subtypes, reflecting the distribution of morphologically and physiologically distinct astrocyte populations. Our analysis identifies five transcriptomically distinct astrocyte subtypes in adult mouse cortex and hippocampus. To investigate the true extent of astrocyte molecular diversity across forebrain regions, we used single-cell RNA sequencing. Crucially, emerging evidence shows specific adaptations and astrocyte-encoded functions in regions, such as the spinal cord and cerebellum. 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. ![]()
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