Spatiotemporal heterogeneity and protective polarization of astrocytes depending on intercellular interaction after intracerebral hemorrhage

Abstract Multiple cells and their interactions in the perihematomal lesions play crucial roles in the progression of intracerebral hemorrhage (ICH), but full dynamics of intercellular interactions among the resident and peripheral cells remain incompletely characterized. Here we provided a dynamic single-cell transcriptome landscape of the perihematomal lesions from ICH mice. Astrocytes emerged as the primary signal recipients in the cell-cell communication network, exhibiting spatiotemporal diversity with six identified subtypes surrounding the hematoma in both ICH mice and patients. Notably, A2, A-glia, and A-regen subtypes of astrocytes dominantly formed the palisading astrocyte scar at day 7 post-ICH exerting neuroprotection and brain repair. The ligand-receptor pair PSAP-GPR37L1, dominant in incoming signaling of astrocytes post-ICH, was essential in astrocyte scar formation and protective polarization, thus mitigating brain injury. Overall, our study provided a comprehensive profile of intercellular interactions in perihematomal lesions following ICH and highlighted astrocyte heterogeneity in the pathologic processes and early intervention.