Abstract
Pericytes are multipotent perivascular cells that play important roles in CNS injury. However, controversial findings exist on how pericytes change and whether they differentiated into microglia-like cells after ischemic stroke. This discrepancy is mainly due to the lack of pericyte-specific markers: the "pericyte" population identified in previous studies contained vascular smooth muscle cells (vSMCs) and/or fibroblasts. Therefore, it remains unclear which cell type differentiates into microglia-like cells after stroke. In this study, lineage-tracing technique was used to mark α-smooth muscle actin (SMA)low/undetectable pericytes, vSMCs, and fibroblasts, and their fates were analyzed after ischemic stroke. We found that SMAlow/undetectable pericytes and fibroblasts but not vSMCs substantially proliferated at the subacute phase after injury, and that SMAlow/undetectable pericyte but not vSMCs or fibroblasts differentiated into Iba1+ cells after ischemic stroke. Further imaging flow cytometry analysis revealed that SMAlow/undetectable pericytes differentiated into both microglia and macrophages at day 7 after stroke. These results demonstrate that SMAlow/undetectable pericytes rather than vSMCs or fibroblasts differentiate into both microglia-like and macrophage-like cells after stroke, suggesting that these pericytes may be targeted in the treatment of ischemic stroke.