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Astrocyte heterogeneity reveals region-specific astrogenesis in the white matter

Bocchi, Riccardo, Thorwirth, Manja, Simon-Ebert, Tatiana, Koupourtidou, Christina, Clavreul, Solène, Kolf, Keegan, Della Vecchia, Patrizia, Bottes, Sara, Jessberger, Sebastian, Zhou, Jiafeng, Wani, Gulzar, Pilz, Gregor-Alexander, Ninkovic, Jovica, Buffo, Annalisa, Sirko, Swetlana, Götz, Magdalena, Fischer-Sternjak, Judith·2025·Nature Neuroscience
DOI 10.1038/s41593-025-01878-6PMC PMC11893471
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Abstract

Astrocyte heterogeneity has been well explored, but our understanding of white matter (WM) astrocytes and their distinctions from gray matter (GM) astrocytes remains limited. Here, we compared astrocytes from cortical GM and WM/corpus callosum (WM/CC) using single-cell RNA sequencing 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 we compared murine astrocytes from two different WM regions, the cortex and cerebellum, we found that they exhibited 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 the WM/CC, but not in the cerebellar WM, suggesting that the WM/CC may be a source of continued astrogenesis.

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  1. Bass, N. H., Hess, H. H., Pope, A. & Thalheimer, C. Quantitative cytoarchitectonic distribution of neurons, glia, and DNA in rat cerebral cortex. J. Comp. Neurol. 143, 481–490 (1971). · DOI
  2. Barres, B. A. The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 60, 430–440 (2008). · DOI · Paper page
  3. Chai, H. et al. Neural circuit-specialized astrocytes: transcriptomic, proteomic, morphological, and functional evidence. Neuron 95, 531–549 (2017). · DOI · Paper page
  4. Ramón y Cajal, S. Histology of the Nervous System of Man and Vertebrates (Oxford Univ. Press, 1995). · DOI
  5. Lanjakornsiripan, D. et al. Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers. Nat. Commun. 9, 1623 (2018). · DOI
  6. Matyash, V. & Kettenmann, H. Heterogeneity in astrocyte morphology and physiology. Brain Res. Rev. 63, 2–10 (2010). · DOI
  7. Miller, R. H. & Raff, M. C. Fibrous and protoplasmic astrocytes are biochemically and developmentally distinct. J. Neurosci. 4, 585–592 (1984). · DOI
  8. Köhler, S., Winkler, U. & Hirrlinger, J. Heterogeneity of astrocytes in grey and white matter. Neurochem. Res. 46, 3–14 (2021). · DOI · Paper page
  9. Bayraktar, O. A. et al. Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map. Nat. Neurosci. 23, 500–509 (2020). · DOI · Paper page
  10. Lozzi, B., Huang, T.-W., Sardar, D., Huang, A. Y.-S. & Deneen, B. Regionally distinct astrocytes display unique transcription factor profiles in the adult brain. Front. Neurosci. 14, 61 (2020). · DOI · Paper page
  11. Morel, L. et al. Molecular and functional properties of regional astrocytes in the adult brain. J. Neurosci. 37, 8706–8717 (2017). · DOI · Paper page
  12. Ohlig, S. et al. Molecular diversity of diencephalic astrocytes reveals adult astrogenesis regulated by Smad4. EMBO J. 40, e107532 (2021). · DOI
  13. Schneider, J. et al. Astrogenesis in the murine dentate gyrus is a life-long and dynamic process. EMBO J. 41, e110409 (2022). · DOI
  14. Sohn, J. et al. The subventricular zone continues to generate corpus callosum and rostral migratory stream astroglia in normal adult mice. J. Neurosci. 35, 3756–3763 (2015). · DOI
  15. Fleming, S. J. et al. Unsupervised removal of systematic background noise from droplet-based single-cell experiments using CellBender. Nat. Methods 20, 1323–1335 (2023). · DOI · Paper page
  16. Beckervordersandforth, R. et al. In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells. Cell Stem Cell 7, 744–758 (2010). · DOI · Paper page
  17. Mizrak, D. et al. Single-cell analysis of regional differences in adult V-SVZ neural stem cell lineages. Cell Rep. 26, 394–406(2019). · DOI · Paper page
  18. Kalamakis, G. et al. Quiescence modulates stem cell maintenance and regenerative capacity in the aging brain. Cell 176, 1407–1419 (2019). · DOI · Paper page
  19. El Amri, M., Fitzgerald, U. & Schlosser, G. MARCKS and MARCKS-like proteins in development and regeneration. J. Biomed. Sci. 25, 43 (2018). · DOI
  20. Zhang, Y.-Y. et al. A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption. Science 360, 1087–1092 (2018). · DOI
  21. Köhler, S. et al. Gray and white matter astrocytes differ in basal metabolism but respond similarly to neuronal activity. Glia 71, 229–244 (2023). · DOI
  22. Koupourtidou, C. et al. Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex. Nat. Commun. 15, 2866 (2024). · DOI · Paper page
  23. Farioli-Vecchioli, S. et al. Tis21 is required for adult neurogenesis in the subventricular zone and for olfactory behavior regulating cyclins, BMP4, Hes1/5 and Ids. Front. Cell. Neurosci. 8, 98 (2014). · DOI
  24. Maynard, K. R. et al. Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex. Nat. Neurosci. 24, 425–436 (2021). · DOI · Paper page
  25. Heinrich, C. et al. Generation of subtype-specific neurons from postnatal astroglia of the mouse cerebral cortex. Nat. Protoc. 6, 214–228 (2011). · DOI
  26. Pilz, G.-A. et al. Live imaging of neurogenesis in the adult mouse hippocampus. Science 359, 658–662 (2018). · DOI
  27. Bottes, S. & Jessberger, S. Live imaging of remyelination in the adult mouse corpus callosum. Proc. Natl Acad. Sci. USA 118, e2025795118 (2021). · DOI
  28. Di Bella, D. J. et al. Molecular logic of cellular diversification in the mouse cerebral cortex. Nature 595, 554–559 (2021). · DOI · Paper page
  29. Endo, F. et al. Molecular basis of astrocyte diversity and morphology across the CNS in health and disease. Science 378, eadc9020 (2022). · DOI
  30. Hamilton, N. et al. Mechanisms of ATP- and glutamate-mediated calcium signaling in white matter astrocytes. Glia 56, 734–749 (2008). · DOI
  31. Lezmy, J. et al. Astrocyte Ca2+-evoked ATP release regulates myelinated axon excitability and conduction speed. Science 374, eabh2858 (2021). · DOI
  32. Werkman, I. L. et al. Transcriptional heterogeneity between primary adult grey and white matter astrocytes underlie differences in modulation of in vitro myelination. J. Neuroinflammation 17, 373 (2020). · DOI
  33. Hassel, B., Boldingh, K. A., Narvesen, C., Iversen, E. G. & Skrede, K. K. Glutamate transport, glutamine synthetase and phosphate-activated glutaminase in rat CNS white matter. A quantitative study. J. Neurochem. 87, 230–237 (2003). · DOI
  34. Li, D., Ropert, N., Koulakoff, A., Giaume, C. & Oheim, M. Lysosomes are the major vesicular compartment undergoing Ca2+-regulated exocytosis from cortical astrocytes. J. Neurosci. 28, 7648–7658 (2008). · DOI
  35. De León Reyes, N. S., Bragg-Gonzalo, L. & Nieto, M. Development and plasticity of the corpus callosum. Development 147, dev189738 (2020). · DOI
  36. García-Martinez, Y., Sánchez-Huerta, K. B. & Pacheco-Rosado, J. Quantitative characterization of proliferative cells subpopulations in the hilus of the hippocampus of adult Wistar rats: an integrative study. J. Mol. Histol. 51, 437–453 (2020). · DOI
  37. Karpf, J. et al. Dentate gyrus astrocytes exhibit layer-specific molecular, morphological and physiological features. Nat. Neurosci. 25, 1626–1638 (2022). · DOI
  38. Seeker, L. A. et al. Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function. Acta Neuropathol. Commun. 11, 84 (2023). · DOI
  39. Tien, A.-C. et al. Regulated temporal-spatial astrocyte precursor cell proliferation involves BRAF signalling in mammalian spinal cord. Development 139, 2477–2487 (2012). · DOI
  40. Nakamura, T., Colbert, M. C. & Robbins, J. Neural crest cells retain multipotential characteristics in the developing valves and label the cardiac conduction system. Circ. Res. 98, 1547–1554 (2006). · DOI
  41. Kim, E. J., Ables, J. L., Dickel, L. K., Eisch, A. J. & Johnson, J. E. Ascl1 (Mash1) defines cells with long-term neurogenic potential in subgranular and subventricular zones in adult mouse brain. PLoS ONE 6, e18472 (2011). · DOI
  42. Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140 (2010). · DOI · Paper page
  43. Tinevez, J.-Y. et al. TrackMate: an open and extensible platform for single-particle tracking. Methods 115, 80–90 (2017). · DOI
  44. Ershov, D. et al. TrackMate 7: integrating state-of-the-art segmentation algorithms into tracking pipelines. Nat. Methods 19, 829–832 (2022). · DOI
  45. Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888–1902 (2019). · DOI · Paper page
  46. Luecken, M. D. & Theis, F. J. Current best practices in single-cell RNA-seq analysis: a tutorial. Mol. Syst. Biol. 15, e8746 (2019). · DOI · Paper page
  47. Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289–1296 (2019). · DOI · Paper page
  48. La Manno, G. et al. RNA velocity of single cells. Nature 560, 494–498 (2018). · DOI · Paper page
  49. Svensson, V. & Pachter, L. RNA velocity: molecular kinetics from single-cell RNA-seq. Mol. Cell 72, 7–9 (2018). · DOI
  50. Jin, S. et al. Inference and analysis of cell–cell communication using CellChat. Nat. Commun. 12, 1088 (2021).

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Metadata

Authors
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.
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2025-02-24
Volume
28
Issue
3
Pages
457-469
ISSN
  • 1097-6256
  • 1546-1726
DOI
10.1038/s41593-025-01878-6
PMC
PMC11893471
Cited by
72
References
12
Language
en
Licence
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (P2GEP3_174900, P400PB_183826, PZ00P3_201995)

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