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Publication : Single-Cell RNA Sequencing and Assay for Transposase-Accessible Chromatin Using Sequencing Reveals Cellular and Molecular Dynamics of Aortic Aging in Mice.

First Author  Xie W Year  2022
Journal  Arterioscler Thromb Vasc Biol Volume  42
Issue  2 Pages  156-171
PubMed ID  34879708 Mgi Jnum  J:356823
Mgi Id  MGI:7762915 Doi  10.1161/ATVBAHA.121.316883
Citation  Xie W, et al. (2022) Single-Cell RNA Sequencing and Assay for Transposase-Accessible Chromatin Using Sequencing Reveals Cellular and Molecular Dynamics of Aortic Aging in Mice. Arterioscler Thromb Vasc Biol 42(2):156-171
abstractText  OBJECTIVE: 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. CONCLUSIONS: Our data provide a system-wide model for transcriptional and epigenetic regulation during aortic aging at single-cell resolution.
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