Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
10
09
2022
accepted:
13
10
2023
pubmed:
9
12
2023
medline:
9
12
2023
entrez:
8
12
2023
Statut:
ppublish
Résumé
The glial environment influences neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models of traumatic brain injury, beneficial functions of proliferating reactive astrocytes on disease outcome have been unraveled, but little is known regarding if and when they are present in human brain pathology. Here we examined a broad spectrum of pathologies with and without intracerebral hemorrhage and found a striking correlation between lesions involving blood-brain barrier rupture and astrocyte proliferation that was further corroborated in an assay probing for neural stem cell potential. Most importantly, proteomic analysis unraveled a crucial signaling pathway regulating this astrocyte plasticity with GALECTIN3 as a novel marker for proliferating astrocytes and the GALECTIN3-binding protein LGALS3BP as a functional hub mediating astrocyte proliferation and neurosphere formation. Taken together, this work identifies a therapeutically relevant astrocyte response and their molecular regulators in different pathologies affecting the human cerebral cortex.
Identifiants
pubmed: 38066208
doi: 10.1038/s41591-023-02644-6
pii: 10.1038/s41591-023-02644-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3149-3161Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 408885537
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 405358801
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 390857198
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 874758
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 885382
Informations de copyright
© 2023. The Author(s).
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