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In the mature cerebellum astrocytes with different morphologies occupy distinct cerebellar territories. This enables their classification into 4 distinct types based on their morphology and topographical localization. Such a well-defined classification offers an excellent platform to challenge the concept of astrocyte heterogeneity as well as to attempt cross-correlating the multilevel expression of such diversity.
Through single-cell RNA sequencing of the adult mouse cerebellum, we shed light to an unprecedented degree of transcriptional heterogeneity within cerebellar astrocytes and uncovered the transcriptional profiles of nine distinct astrocyte subtypes, whose regional segregation was unveiled by spatial transcriptomics.
Many of these subtypes showed strong enrichment in one cerebellar layer, enabling us to confirm the correspondence between morphologically and topographically cell classes and transcriptional heterogeneity. Of note, among the four identified BG subtypes, two showed complementary distributions along the anteroposterior axis. Some subtypes instead showed enrichment in multiple layers. Among them, a subtype localized in the Purkinje cell layer and in the white matter showed transcriptional features similar to progenitors. Another subgroup of cells, spanning both the cerebellar cortex and white matter, showed an enrichment in terms suggesting their involvement in vesicular gliotransmission and synaptic communication. While these clusters highlighted specialized functional traits, the overall transcriptional heterogeneity among all nine profiles underscored a predominant broad functional divergence between BG and non-BG astrocytes. BG transcriptional signature confirmed their specialization in interacting with Purkinje cells and modulating their synaptic inputs, while the other non-BG astrocytes displayed enrichment for genes that pointed to their novel potential roles in energy homeostasis via regulation of blood supply,glucose and glycogen metabolism and in neuroprotection.These findings set the stage for investigating cerebellar astrocyte heterogeneity in diseased conditions and for comparative studies between mouse and human cerebellum.
| Author(s) | Turrini G*, Cerrato V*, Vitali I, Xiong B, Solanelles-Farré L, Lopes A, Magrinelli E, Bocchi R, Fischer J, Götz M5, Telley L & Buffo A |
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| Affiliation(s) | "Dept. of Neuroscience R. Levi Montalcini, UniTo, Italy, Dept. of Neuroscience R. Levi Montalcini, UniTo, Italy, Dept of Fundamental Neuroscience, UniL, Switzerland, Dept of Fundamental Neuroscience, UniL, Switzerland, Dept of Fundamental Neuroscience, UniL, Switzerland, Dept of Fundamental Neuroscience, UniL, Switzerland, Dept of Fundamental Neuroscience, UniL, Switzerland, Dept of Basic Neuroscience, UniGe, Switzerland, Helmholtz Zentrum München, Germany, Dept of Fundamental Neuroscience, UniL, Switzerland, Dept. of Neuroscience R. Levi Montalcini, UniTo, Italy" |
