Single-cell transcriptional and epigenetic dynamics during aortic aging in mice

The impact of vascular aging (VA) has been extensively studied, yet little is known regarding the cellular and molecular mechanism underlying age-related VA in aortic cellular subpopulations. Herein, we analyzed transcriptomes and transposase-accessible chromatin profiles from aortas of 4-, 26-, and 86-week-old mice using single-cell RNA sequencing and ATAC sequencing. By integrating the heterogeneous transcriptome and chromatin accessibility data, we identified cell-specific transcription factor (TF) regulatory networks and open chromatin states. Moreover, we found that aortic aging affects cell interactions, inflammation, cell type composition and dysregulation of transcriptional control. Endothelial cell (EC) 1 has higher gene set activity related to senescence, aging, and adipogenesis than EC 2. Construction of senescence trajectories showed that the senescence of EC 1 and fibroblasts 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. Transcriptomes and transposase-accessible chromatin profiles from aortas of two 4-week-old, two 26-week-old, and two 86-week-old mice血管衰老（vascular aging, VA）的影响已被广泛研究，但目前针对主动脉细胞亚群中年龄相关性血管衰老的细胞与分子机制，仍缺乏深入认知。本研究借助单细胞RNA测序（single-cell RNA sequencing）与ATAC测序（ATAC sequencing），解析了4周龄、26周龄及86周龄小鼠的主动脉转录组与转座酶可及染色质图谱。通过整合异质性转录组与染色质可及性数据，我们鉴定得到细胞特异性转录因子（transcription factor, TF）调控网络与开放染色质状态。此外，本研究发现主动脉衰老可影响细胞间互作、炎症反应、细胞类型组成以及转录调控的失调。内皮细胞（endothelial cell, EC）1的衰老、衰老相关及成脂分化相关基因集活性高于EC 2。衰老轨迹构建结果显示，EC 1与成纤维细胞的衰老过程与独特的TF开放染色质状态及mRNA表达模式紧密关联。本研究数据以单细胞分辨率构建了主动脉衰老过程中转录与表观遗传调控的全系统模型。本数据集包含2只4周龄、2只26周龄及2只86周龄小鼠的主动脉转录组与转座酶可及染色质图谱。