Integrating spatial and single-cell transcriptomics to characterize the molecular and cellular architecture of the ischemic mouse brain.
Sci Transl Med
; 16(733): eadg1323, 2024 Feb 07.
Article
en En
| MEDLINE
| ID: mdl-38324639
ABSTRACT
Neuroinflammation is acknowledged as a pivotal pathological event after cerebral ischemia. However, there is limited knowledge of the molecular and spatial characteristics of nonneuronal cells, as well as of the interactions between cell types in the ischemic brain. Here, we used spatial transcriptomics to study the ischemic hemisphere in mice after stroke and sequenced the transcriptomes of 19,777 spots, allowing us to both visualize the transcriptional landscape within the tissue and identify gene expression profiles linked to specific histologic entities. Cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of ischemia-associated gene expression in the peri-infarct area of the ischemic hemisphere. Analysis of ligand-receptor interactions in cell communication revealed galectin-9 to cell-surface glycoprotein CD44 (LGALS9-CD44) as a critical signaling pathway after ischemic injury and identified microglia and macrophages as the main source of galectins after stroke. Extracellular vesicle-mediated Lgals9 delivery improved the long-term functional recovery in photothrombotic stroke mice. Knockdown of Cd44 partially reversed these therapeutic effects, inhibiting oligodendrocyte differentiation and remyelination. In summary, our study provides a detailed molecular and cellular characterization of the peri-infact area in a murine stroke model and revealed Lgals9 as potential treatment target that warrants further investigation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Isquemia Encefálica
/
Accidente Cerebrovascular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Transl Med
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China