Astrocyte heterogeneity reveals region-specific astrogenesis in the white matter


Astrocyte heterogeneity has been well explored, but our understanding of white matter (WM) astrocytes and their distinctions from grey matter (GM) astrocytes remains limited. Here, we compared astrocytes from cortical GM and WM/corpus callosum (WM/CC) using single cell RNA-sequencing (scRNA-seq) and spatial transcriptomics of the murine forebrain. The comparison revealed similarities, but also significant differences between WM and GM astrocytes, including cytoskeletal and metabolic hallmarks specific to WM astrocytes with molecular properties also shared with human WM astrocytes. When comparing murine astrocytes from two different WM regions, cortex and cerebellum, we found that they exhibit distinct, region-specific molecular properties, with the cerebellum lacking for example a specific cluster of WM astrocytes expressing progenitor and proliferation genes. Functional experiments confirmed astrocyte proliferation in WM/CC, but not cerebellar WM, suggesting that the WM/CC may be a source of continued astrogenesis.

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Cell information / gene expression violin plot / box plot

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Gene Expression

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Cell information / gene expression violin plot / box plot

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Reference: Bocchi, R., Thorwirth, M., Simon-Ebert, T., Koupourtidou, C., Clavreul, S., Kolf, K., Della Vecchia, P., Bottes, S., Jessberger, S., Zhou, J., Wani, G., Pilz, G.-A., Ninkovic, J., Buffo, A., Sirko, S., Götz, M. & Fischer-Sternjak, J.; Nature Neuroscience (2025). doi: 10.1038/s41593-025-01878-6 [Link]

Link to the laboratory webpages: Gotz Lab and Bocchi Lab

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*The picture above was provided by Manja Thorwirth and edited using photo editor Befunky