Department of Geriatrics, Department of Cardiac Surgery, and Department of Cardiology, Fujian Heart Disease Center, Fujian Medical University Union Hospital, Fuzhou, China (W.X., Q.Y., J.L., L.C., J.F., X.C., Y.Z., L.C., H.H.).
Fujian Key Laboratory of Vascular Aging, Fujian Medical University, Fuzhou, China (W.X., Y.K., D.L., H.H.).
Arterioscler Thromb Vasc Biol. 2022 Feb;42(2):156-171. doi: 10.1161/ATVBAHA.121.316883. Epub 2021 Dec 9.
The impact of vascular aging on cardiovascular diseases has been extensively studied; however, little is known regarding the cellular and molecular mechanisms underlying age-related vascular aging in aortic cellular subpopulations. Approach and Results: Transcriptomes and transposase-accessible chromatin profiles from the aortas of 4-, 26-, and 86-week-old C57/BL6J mice were analyzed using single-cell RNA sequencing and assay for transposase-accessible chromatin sequencing. By integrating the heterogeneous transcriptome and chromatin accessibility data, we identified cell-specific TF (transcription factor) regulatory networks and open chromatin states. We also determined that aortic aging affects cell interactions, inflammation, cell type composition, dysregulation of transcriptional control, and chromatin accessibility. Endothelial cells 1 have higher gene set activity related to cellular senescence and aging than do endothelial cells 2. Moreover, construction of senescence trajectories shows that endothelial cell 1 and fibroblast senescence is associated with distinct TF open chromatin states and an mRNA expression model.
Our data provide a system-wide model for transcriptional and epigenetic regulation during aortic aging at single-cell resolution.
血管老化对心血管疾病的影响已得到广泛研究；然而，关于主动脉细胞亚群中与年龄相关的血管老化的细胞和分子机制知之甚少。
使用单细胞 RNA 测序和转座酶可及染色质测序分析了来自 4 周、26 周和 86 周龄 C57/BL6J 小鼠主动脉的转录组和转座酶可及染色质图谱。通过整合异质转录组和染色质可及性数据，我们确定了细胞特异性 TF（转录因子）调控网络和开放染色质状态。我们还确定了主动脉老化会影响细胞间相互作用、炎症、细胞类型组成、转录控制失调和染色质可及性。与内皮细胞 2 相比，内皮细胞 1 具有更高的与细胞衰老和老化相关的基因集活性。此外，衰老轨迹的构建表明，内皮细胞 1 和成纤维细胞的衰老与不同的 TF 开放染色质状态和 mRNA 表达模型相关。
我们的数据提供了一个在单细胞分辨率下系统地研究主动脉老化过程中转录和表观遗传调控的模型。
