The Transcriptional Landscape of Pericytes in Acute Ischemic Stroke

Abstract

The current treatment options for ischemic stroke aim to achieve reperfusion but are time critical. Novel therapeutic approaches that can be given beyond the limited time window of 3-4.5 h are still an unmet need to be addressed to improve stroke outcomes. The lack of oxygen and glucose in the area of ischemic injury initiates a pathological cascade leading to blood-brain barrier (BBB) breakdown, inflammation, and neuronal cell death, a process that may be intercepted to limit stroke progression. Pericytes located at the blood/brain interface are one of the first responders to hypoxia in stroke and therefore a potential target cell for early stroke interventions. Using single-cell RNA sequencing in a mouse model of permanent middle cerebral artery occlusion, we investigated the temporal differences in transcriptomic signatures in pericytes at 1, 12, and 24 h after stroke. Our results reveal a stroke-specific subcluster of pericytes that is present at 12 and 24 h and characterized by the upregulation of genes mainly related to cytokine signaling and immune response. This study identifies temporal transcriptional changes in the acute phase of ischemic stroke that reflect the early response of pericytes to the ischemic insult and its secondary consequences and may constitute potential future therapeutic targets.