Gao Ya-Kun, Guo Rui-Juan, Xu Xin, Huang Xiao-Fu, Song Yu, Zhang Dan-Dan, Chen Ning, Wang Xiao-Wei, Liang Chen-Xi, Kong Peng, Han Mei
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang, China.
Laboratory of Lipid Metabolism, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
PLoS One. 2022 Mar 23;17(3):e0265132. doi: 10.1371/journal.pone.0265132. eCollection 2022.
Vascular smooth muscle cell (VSMC) subpopulations relevant to vascular disease and injury repair have been depicted in healthy vessels and atherosclerosis profiles. However, whether VSMC subpopulation associated with vascular homeostasis exists in the healthy artery and how are their nature and fate in vascular remodeling remains elusive. Here, using single-cell RNA-sequencing (scRNA-seq) to detect VSMC functional heterogeneity in an unbiased manner, we showed that VSMC subpopulations in healthy artery presented transcriptome diversity and that there was significant heterogeneity in differentiation state and development within each subpopulation. Notably, we detected an independent subpopulation of VSMCs that highly expressed regulator of G protein signaling 5 (RGS5), upregulated the genes associated with inhibition of cell proliferation and construction of cytoskeleton compared with the general subpopulation, and mainly enriched in descending aorta. Additionally, the proportion of RGS5high VSMCs was markedly decreased or almost disappeared in the vascular tissues of neointimal formation, abdominal aortic aneurysm and atherosclerosis. Specific spatiotemporal characterization of RGS5high VSMC subpopulation suggested that this subpopulation was implicated in vascular homeostasis. Together, our analyses identify homeostasis-relevant transcriptional signatures of VSMC subpopulations in healthy artery, which may explain the regional vascular resistance to atherosclerosis at some extent.
与血管疾病和损伤修复相关的血管平滑肌细胞（VSMC）亚群已在健康血管和动脉粥样硬化病变中得到描述。然而，健康动脉中是否存在与血管稳态相关的VSMC亚群，以及它们在血管重塑中的性质和命运仍然不清楚。在这里，我们使用单细胞RNA测序（scRNA-seq）以无偏倚的方式检测VSMC功能异质性，结果表明健康动脉中的VSMC亚群呈现转录组多样性，并且每个亚群内的分化状态和发育存在显著异质性。值得注意的是，我们检测到一个独立的VSMC亚群，其高表达G蛋白信号调节因子5（RGS5），与一般亚群相比，上调了与抑制细胞增殖和细胞骨架构建相关的基因，并且主要富集在降主动脉中。此外，在新生内膜形成、腹主动脉瘤和动脉粥样硬化的血管组织中，RGS5高表达的VSMC比例明显降低或几乎消失。RGS5高表达的VSMC亚群的特定时空特征表明该亚群与血管稳态有关。总之，我们的分析确定了健康动脉中与稳态相关的VSMC亚群的转录特征，这可能在一定程度上解释了区域血管对动脉粥样硬化的抗性。
