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 30th day after the vascular injury.
Highlights
Vascular smooth muscle cell (VSMC) accumulation in the neointima is a common feature in vascular diseases such as atherosclerosis, transplant arteriosclerosis, and restenosis
The results showed a clear clustering of the neointimal cells with the peripheral blood mononuclear cells (PBMC)/bone marrow mononuclear cells (BMMC)
When blood vessel is injured, VSMCs dramatically increase their proliferation, migration, and synthetic capacity; the high degree of plasticity can lead to an adverse phenotypic switch and vascular diseases, such as atherosclerosis, restenosis, cancer, and hypertension [38,39]
Summary
Vascular smooth muscle cell (VSMC) accumulation in the neointima is a common feature in vascular diseases such as atherosclerosis, transplant arteriosclerosis, and restenosis. The apparent increase in proliferation among the tunica media cells after injury [3,4,5,6] and the ex vivo development of neointima in arterial culture systems [7,8,9] supported this theory It was further reinforced by the fact that neointimal cells expressed those VSMC markers, such as smooth muscle alpha actin (SMA), and vimentin [10,11,12]. Because the differentiated cells may still remember their origins implemented in their memory via DNA methylation patterns, we sought to compare the DNA methylation profiles between neointimal cells, residential VSMCs and bone marrow derived circulating progenitor cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Molecular biology (Los Angeles, Calif.)
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
