title: DNA Methylation Signature of Post-injury Neointimal Cells During Vascular Remodeling in the Rat Balloon Injury Model.
abstract: Vascular smooth muscle cell (VSMC) accumulation in the neointimal is a common feature in vascular diseases such as atherosclerosis, transplant arteriosclerosis and restenosis. In this study, we isolated the neointimal cells and uninjured residential vascular smooth muscle cells by laser micro dissection and carried out single-cell whole-genome methylation sequencing. We also sequenced the bisulfite converted genome of circulating bone-marrow-derived cells such as peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC). We found totally 2,360 differential methylation sites (DMS) annotated to 1,127 gene regions. The majority of differentially methylated regions (DMRs) were located in intergenic regions, outside those CpG islands and island shores. Interestingly, exons have less DMRs than promotors and introns, and CpG islands contain more DMRs than islands shores. Pearson correlation analysis showed a clear clustering of neointimal cells with PBMC/BMMC. Gene set enrichment analysis of differentially methylated CpG sites revealed that many genes were important for regulation of VSMC differentiation and stem cell maintenance. In conclusion, our results showed that neointimal cells are more similar to the progenitor cells in methylation profile than the residential VSMCs at the 30thday after the vascular injury.
authors.affiliation: Cardiovascular Research Institute and Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Jendai
authors.initials: J
authors.lastname: Richards
authors.affiliation: Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Henry Ato
authors.initials: HA
authors.lastname: Ogoe
authors.affiliation: Cardiovascular Research Institute and Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Li
authors.affiliation: Cardiovascular Research Institute and Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Oguljahan
authors.initials: O
authors.lastname: Babayewa
authors.affiliation: Cardiovascular Research Institute and Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Cardiovascular Research Institute and Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Tameka
authors.initials: T
authors.lastname: Bythwood
authors.affiliation: Cardiovascular Research Institute and Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Minerva
authors.initials: M
authors.lastname: Garcia-Barrios
authors.affiliation: Cardiovascular Research Institute and Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia, USA; 4DGenome Inc, Atlanta, Georgia, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Cardiovascular Research Institute and Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia, USA; 4DGenome Inc, Atlanta, Georgia, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Song
keywords: Atherosclerosis; Biomarkers; DNA Methylation