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