Pericytes are a heterogeneous population of mural cells that surround microvessels in various organs including the heart and brain. Their function, beyond maintaining vascular integrity and contractility, is poorly understood. Recent studies have suggested they contribute to the development of tissue fibrosis. 1 For instance, after spinal cord injury, a subpopulation of pericytes divide and migrate away from blood vessels, where they form the fibrotic scar that constitutes the lesion cavity. 2 Although recent studies suggest pericyte function in homeostasis and after organ injury, their role in mediating fibrosis after vascular ischemia in the heart and brain is not firmly established, owing to differences in injury models, labeling techniques, and transgenic models. 3–5 We explored the role of pericytes after myocardial infarction (MI) and ischemic stroke by interrogating their gene expression at a single-cell level and their contribution to tissue fibrosis in parallel studies. We used a double transgenic mouse model, Tbx18CreER/+; Rosa26 tdT/+, 4 to lineage-trace TBX18 (T-box transcription factor 18)-expressing pericytes and define their location, fate, and gene expression profiles at a single-cell resolution during homeostasis and after MI and stroke. Male 2-to 3-month-old mice received 1 mg of tamoxifen intraperitoneally for 4 consecutive days, followed by a 1-week washout period. They then underwent MI (by permanent ligation of the left anterior descending artery), stroke (by photothrombosis), or sham surgery. Seven days later, when initial fibrosis appears in either model, tdTomatolabeled cells were isolated from uninjured and ischemic hearts and brains by fluorescence-activated cell sorting. Before sorting pericytes from the injured organs, the core infarct and peri-infarct regions were prepared separately to distinguish pericytes that may be undergoing a transition into a fibrotic state. The isolated cells were then processed for single-cell RNA sequencing, resulting in a transcriptomic dataset consisting of 37 001 cells from the heart and 15 353 cells from the brain (Figure [A]). Other cell types (ie, endothelial cells, fibroblasts, smooth muscle cells, leukocytes) were excluded from our analysis. Pericytes were identified based on expression of known markers, such as Rgs5, Mcam,