Gene expression profiles of endothelium, microglia and oligodendrocytes in hippocampus of post-stroke depression rat at single cell resolution

Abstract

Abstract Post-stroke depression (PSD) is a common but severe mental complication after stroke. However, the cellular and molecular understanding of PSD is still yet to be illustrated. In current study, we prepared PSD rat model (MD) via unilateral middle cerebral artery occlusion (MCAO) and chronic stress stimulation (DEPR), and isolated hippocampal tissues for single cell sequencing of 10x Genomics Chromium. First, we determined the presence of the increased cell population of endothelium and microglia and the compromised oligodendrocytes in MD compared to NC, MCAO and DEPR. The enriched functions of highly variable genes (HVGs) of endothelium and microglia suggested a reinforced blood-brain barrier in MD. Next, cell clusters of endothelium, microglia and oligodendrocytes were individually analyzed, and the subtypes with distinct functions were identified. The genotype of PSD displayed more similarity with DEPR compared to MCAO and NC. For endothelium, the absence of cell differentiation, but robust proliferation and fibrosis instead were observed in MD. For microglia, multiple subpopulations showed the superimposition of neurotoxic and neuroprotective functions, and DEPR could enlarge the effect of microglia in MCAO. For oligodendrocytes, the one for demyelination were elevated in DEPR and MD, while the one for remyelination were robust in MCAO, and the oligodendrocytes undergoing demyelination were processed via apoptosis, autophagy and ferroptosis manner. Finally, we also observed that the intercellular crosstalk among these three cells were largely elevated in MACO but compromised in DEPR, whereas was intermediate between them in MD, and depression and stroke could both activate the inflammation reaction but through different signals. Taken together, this study characterized the single cell expression profile of hippocampal PSD, and unmask the differential expressed genes of endothelium, microglia and oligodendrocytes, emphasizing the crosstalk among them to provide theoretical basis for the in-depth mechanism research and drug therapy of PSD.