0603202 - ÚEM 2025 RIV US eng J - Journal Article
Žucha, D. - Abaffy, P. - Kirdajová, Denisa - Jirák, D. - Kubista, M. - Anděrová, Miroslava - Valihrach, L.
Spatiotemporal transcriptomic map of glial cell response in a mouse model of acute brain ischemia.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 121, č. 46 (2024), č. článku e2404203121. ISSN 0027-8424. E-ISSN 1091-6490
R&D Projects: GA MŠMT(CZ) LM2023050; GA ČR(CZ) GA23-05327S; GA ČR(CZ) GA23-06269S
Grant - others:AV ČR(CZ) StrategieAV21/29
Program: StrategieAV
Institutional support: RVO:68378041
Keywords : ischemic stroke * single-cell transcriptomics * spatial transcriptomics * glia * neuroinflammation
OECD category: Neurosciences (including psychophysiology
Impact factor: 9.4, year: 2023 ; AIS: 4.352, rok: 2023
Method of publishing: Open access
Result website:
https://www.pnas.org/doi/10.1073/pnas.2404203121DOI: https://doi.org/10.1073/pnas.2404203121

The role of nonneuronal cells in the resolution of cerebral ischemia remains to be fully understood. To decode key molecular and cellular processes that occur after ischemia, we performed spatial and single-cell transcriptomic profiling of the male mouse brain during the first week of injury. Cortical gene expression was severely disrupted, defined by inflammation and cell death in the lesion core, and glial scar formation orchestrated by multiple cell types on the periphery. The glial scar was identified as a zone with intense cell–cell communication, with prominent ApoE-Trem2 signaling pathway modulating microglial activation. For each of the three major glial populations, an inflammatory-responsive state, resembling the reactive states observed in neurodegenerative contexts, was observed. The recovered spectrum of ischemia-induced oligodendrocyte states supports the emerging hypothesis that oligodendrocytes actively respond to and modulate the neuroinflammatory stimulus. The findings are further supported by analysis of other spatial transcriptomic datasets from different mouse models of ischemic brain injury. Collectively, we present a landmark transcriptomic dataset accompanied by interactive visualization that provides a comprehensive view of spatiotemporal organization of processes in the postischemic mouse brain.
Permanent Link: https://hdl.handle.net/11104/0360440


Research data: Github