Single-Cell Transcriptome Reveals Cell Type–Specific Molecular Pathology in a 2VO Cerebral Ischemic Mouse Model

Post-ischemia memory impairment is a major sequela in cerebral ischemia patients. However, cell type-specific molecular pathology in the hippocampus after ischemia is poorly understood. In this study, we adopted a mouse two-vessel occlusion ischemia model (2VO model) to mimic cerebral ischemia-induced memory impairment and investigated the single-cell transcriptome in the hippocampi in 2VO mice. A total of 27,069 cells were corresponding 14 cell types with neuronal, glial, and vascular lineages. We next analyzed cell-specific gene alterations in 2VO mice and the function of these cell-specific genes. Differential expression analysis identified cell type-specific genes with altered expression in neurons, astrocytes, microglia, and oligodendrocytes in 2VO mice. Notably, four subtypes of oligodendrocyte precursor cells with distinct differentiation pathways were suggested. Taken together, this is the first single-cell transcriptome analysis of gene expression in a 2VO model. Furthermore, we suggested new types of oligodendrocyte precursor cells with angiogenesis and neuroprotective potential, which might offer opportunities to identify new avenues of research and novel targets for ischemia treatment.