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Publication : Neuroinflammatory astrocyte subtypes in the mouse brain.

First Author  Hasel P Year  2021
Journal  Nat Neurosci Volume  24
Issue  10 Pages  1475-1487
PubMed ID  34413515 Mgi Jnum  J:323398
Mgi Id  MGI:7263123 Doi  10.1038/s41593-021-00905-6
Citation  Hasel P, et al. (2021) Neuroinflammatory astrocyte subtypes in the mouse brain. Nat Neurosci 24(10):1475-1487
abstractText  Astrocytes undergo an inflammatory transition after infections, acute injuries and chronic neurodegenerative diseases. How this transition is affected by time and sex, its heterogeneity at the single-cell level and how sub-states are spatially distributed in the brain remains unclear. In this study, we investigated transcriptome changes of mouse cortical astrocytes after an acute inflammatory stimulus using the bacterial cell wall endotoxin lipopolysaccharide. We identified fast transcriptomic changes in astrocytes occurring within hours that drastically change over time. By sequencing ~80,000 astrocytes at single-cell resolution, we show that inflammation causes a widespread response with subtypes of astrocytes undergoing distinct inflammatory transitions with defined transcriptomic profiles. We also attribute key sub-states of inflammation-induced reactive astrocytes to specific brain regions using spatial transcriptomics and in situ hybridization. Together, our datasets provide a powerful resource for profiling astrocyte heterogeneity and will be useful for understanding the biological importance of regionally constrained reactive astrocyte sub-states.
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