Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC8, Tampa, FL, 33612, USA.
Cell Mol Life Sci. 2022 Apr 28;79(5):264. doi: 10.1007/s00018-022-04322-1.
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) pericytes, vSMCs, and fibroblasts, and their fates were analyzed after ischemic stroke. We found that SMA pericytes and fibroblasts but not vSMCs substantially proliferated at the subacute phase after injury, and that SMA pericyte but not vSMCs or fibroblasts differentiated into Iba1 cells after ischemic stroke. Further imaging flow cytometry analysis revealed that SMA pericytes differentiated into both microglia and macrophages at day 7 after stroke. These results demonstrate that SMA 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.
周细胞是多能的血管周细胞，在中枢神经系统损伤中发挥重要作用。然而，关于周细胞如何变化以及它们在缺血性中风后是否分化为小胶质细胞样细胞，存在争议的发现。这种差异主要是由于缺乏周细胞特异性标志物：以前的研究中鉴定的“周细胞”群体包含血管平滑肌细胞（vSMCs）和/或成纤维细胞。因此，尚不清楚哪种细胞类型在中风后分化为小胶质细胞样细胞。在这项研究中，使用谱系追踪技术标记α-平滑肌肌动蛋白（SMA）周细胞、vSMCs 和成纤维细胞，并分析它们在缺血性中风后的命运。我们发现，SMA 周细胞和成纤维细胞而非 vSMCs 在损伤后的亚急性期大量增殖，并且只有 SMA 周细胞而非 vSMCs 或成纤维细胞在缺血性中风后分化为 Iba1 细胞。进一步的成像流式细胞术分析显示，SMA 周细胞在中风后第 7 天分化为小胶质细胞和巨噬细胞。这些结果表明，SMA 周细胞而非 vSMCs 或成纤维细胞在中风后分化为小胶质细胞样和巨噬细胞样细胞，提示这些周细胞可能成为缺血性中风治疗的靶点。
