Astrocyte heterogeneity reveals region-specific astrogenesis in the white matter

Article Article scientifique Article Astrocyte heterogeneity reveals region-specific astrogenesis in the white matter eng 2025-02-24 2025-03 author Bocchi Riccardo 0000-0002-4105-6807 Chair of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany. riccardo.bocchi@unige.ch.,Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany. riccardo.bocchi@unige.ch.,Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. riccardo.bocchi@unige.ch. 634138 Département de neurosciences fondamentales (NEUFO) author Thorwirth Manja 0000-0002-7692-546X Chair of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany.,Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany. author Simon-Ebert Tatiana Chair of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany.,Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany. author Koupourtidou Christina Chair of Cell Biology and Anatomy, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany. author Clavreul Solène 0000-0001-5384-8425 Chair of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany.,Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany. author Kolf Keegan 0009-0003-9896-6101 Chair of Cell Biology and Anatomy, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany. 987544 author Della Vecchia Patrizia 0009-0001-5623-4581 Chair of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany. author Bottes Sara Laboratory of Neural Plasticity, Brain Research Institute, University of Zurich, Zurich, Switzerland. author Jessberger Sebastian 0000-0002-0056-8275 Laboratory of Neural Plasticity, Brain Research Institute, University of Zurich, Zurich, Switzerland. author Zhou Jiafeng 0009-0005-5056-3762 Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. 989873 Département de neurosciences fondamentales (NEUFO) author Wani Gulzar 0000-0003-2380-5816 Chair of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany.,Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany. author Pilz Gregor-Alexander 0000-0002-6161-4976 Chair of Cell Biology and Anatomy, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany. author Ninkovic Jovica Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.,Chair of Cell Biology and Anatomy, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany. author Buffo Annalisa 0000-0001-7637-0006 Department of Neuroscience Rita Levi-Montalcini, University of Turin, Turin, Italy.,Neuroscience Institute Cavalieri Ottolenghi, University of Turin, Orbassano, Italy. author Sirko Swetlana 0000-0001-5950-616X Chair of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany.,Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany. author Götz Magdalena 0000-0003-1551-9203 Chair of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany. magdalena.goetz@helmholtz-munich.de.,Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany. magdalena.goetz@helmholtz-munich.de.,Excellence Cluster of Systems Neurology (SyNergy), Munich, Germany. magdalena.goetz@helmholtz-munich.de. author Fischer-Sternjak Judith 0000-0003-0398-7720 Chair of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany. judith.fischer@helmholtz-munich.de.,Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany. judith.fischer@helmholtz-munich.de. 457-469 10.1038/s41593-025-01878-6 39994409 1097-6256 PMC11893471 https://www.nature.com/articles/s41593-025-01878-6 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. Animals Astrocytes / cytology Astrocytes / metabolism Astrocytes / physiology Cell Proliferation Cerebellum / cytology Cerebral Cortex / cytology Corpus Callosum / cytology Gray Matter / cytology Gray Matter / metabolism Humans Male Mice Mice, Inbred C57BL Neurogenesis / physiology Single-Cell Analysis White Matter / cytology White Matter / metabolism White Matter / physiology Dewey 616.8 Swiss National Science Foundation Functional integration of in vivo reprogrammed neurons after traumatic brain injury 183826 CH Careers European Commission Novel mechanisms of neurogenesis- from centrosome to engineering migration 885382 NeuroCentro EU H2020 European Commission Novel Strategies for Cell-based Neural Reconstruction 874758 NSC-Reconstruct EU H2020 Swiss National Science Foundation Functional integration of in vivo reprogrammed neurons after traumatic brain injury 174900 CH Careers Swiss National Science Foundation Origin and diversity of neocortical astrocytes 201995 CH Careers 53 Département de neurosciences fondamentales 21A false Nature neuroscience 28 3 faa97af4-a6b8-4996-a035-30aeec7ce6ea Article (Published version) Public Article_scientifique_from_unpaywall.pdf 12343632 application/pdf CC BY-4.0 81b310125112d68c9c396bf71cf4e5883c95a4ad542cb27851c392f14cca8332 f90748eb-baa3-4bdc-b7bb-a21d540cecac Supplemental data Public 41593_2025_1878_MOESM2_ESM.xlsx 18602 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 3ff3b0baf5d97c95edcb6ca8a330d8def30b1c5db4dae5ceb9e8ff9a704f0d98 634808c3-a69a-4aae-81d4-77b874141423 Supplemental data Public 41593_2025_1878_MOESM3_ESM.xlsx 355063 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 237858d64721a0dba625a112b5b733e1a132acb820f0fceb173407457fd15875 e1003048-08f2-42a8-8de1-4da3cd9c1670 Supplemental data Public 41593_2025_1878_MOESM4_ESM.xlsx 83890 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 72f0fe949ffa2e5a7ea41f883dbe2ac4d3b5dd24bd87dfde6d02fba89246027e 08489d0e-8285-4e56-9af9-4da3ff85a610 Supplemental data Public 41593_2025_1878_MOESM5_ESM.xlsx 265123 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 382af14d11a04fec44bfe05700885c1392ec55ad620e766a667ec28662edaf44 c2ce23d9-ba1a-443e-8780-1eb6a7beb403 Supplemental data Public 41593_2025_1878_MOESM6_ESM.xlsx 15611 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 979122a15dec64e63525367fa66d0874c63a30a6e8d3ef32d00d32b580c1ae56 102313ad-d6c8-44c7-875e-69a02a567b80 Supplemental data Public 41593_2025_1878_MOESM7_ESM.xlsx 173039 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet f6eecc3b1abbdc2a4d1a16395c2cd0b160f7462f64afeac982a9014ed47d6644 f7390a0e-1ad4-4ffa-9dbb-d02494001fea Supplemental data Public 41593_2025_1878_MOESM8_ESM.xlsx 245621 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 68306c54203f720a1ef591ef0c05c7e79b0c80e26410fa85b897fea2f20ae89d b2b35f7b-143b-4080-ab87-47c4580b0695 Supplemental data Public 41593_2025_1878_MOESM9_ESM.xlsx 15920 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 8c28a70befb130b5f2937b11b8579ced1f6378d40629da9c30ee19b61d6af0a4 9872488b-2143-4240-8dac-1e2b202d3d03 Supplemental data Public 41593_2025_1878_MOESM10_ESM.xlsx 352851 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 01578e7f3c6d853aa253a9311016d21c52ad127ff67404386d09935c473c870f 2101139a-d0bd-4895-898b-0fab29a4ff3a Supplemental data Public 41593_2025_1878_MOESM11_ESM.xlsx 22622 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 237738acd1a3df8409b2acea23427730f94a7c70c983ae5a09db9a4037717aab 56513498-ae22-494a-a634-edada814e5ce Supplemental data Public 41593_2025_1878_MOESM12_ESM.xlsx 30228 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 602d5fee78bd5ae88a284d64d9cd53393f6acd9aa5fd978d7674080896326e51 4f004956-1bdb-4cfe-a38b-2bf582297ff3 Supplemental data Public 41593_2025_1878_MOESM13_ESM.xlsx 11365 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 5d6a9e35cc925ccbec61abb1ed78e10945baa9700b80b428bdd065752251f406 1b7d86e9-f0ca-4036-8b54-6ae1ba736632 Supplemental data Public 41593_2025_1878_MOESM14_ESM.xlsx 12318 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet f6766c191d8d56e515c1ec2f9e586016e4c99ab372d95e8cfa930790db374e25 60ec1ac2-aada-4db1-8792-d8a43c1dbc90 Supplemental data Public 41593_2025_1878_MOESM15_ESM.xlsx 17090 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 79ef9efd82885d66d10d0769ad9e5d3b7c368d6eec67fbaa9ee26c4e49346d19 openAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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Astrocyte heterogeneity reveals region-specific astrogenesis in the white matter	Nature neuroscience			2025	38	67

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Kolf, Keegan