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Epigenome analysis of aging muscle progenitors

ABSTRACT: Genome wide DNA methylation profiling of muscle cells extracted from healthy donors at different ages. The Illumina Infinium Human Methylation 450 BeadChip was used to obtain DNA methylation profiles across > 485,000 methylation sites. The muscle cells were extracted from young adults (18-40 years old) and elderly (>70 years old)(n=3 per group, 2 groups : Young and aged adult).

ORGANISM(S): Homo sapiens

PROVIDER: GSE53302 | GEO | 2015/05/01

SECONDARY ACCESSION(S): PRJNA231630

REPOSITORIES: GEO

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Project description:The ascending aorta is a common site for age-related aortic diseases. Therefore, age-related changes in the cellular composition and development in the normal human ascending aorta tissue is associated with the pathogenesis of aortic diseases. In this study, we performed single-cell transcriptome sequencing of the normal ascending aorta tissues from 6 organ donors of different ages, namely, the young group (3 months, 1 year, 3 years, and 12 years) and the old group (57 years and 58 years), and evaluated the changes in the composition of the cell types, cellular phenotypes, and the cell-cell communication. The single-cell sequencing data analysis of 65,470 cells from the 6 donor aortic wall specimens identified ten cell types (27 high-resolution subtypes of cells), including endothelial cells, smooth muscle cells, fibroblasts, mesenchymal cells, mesenchymal-fibroblast cells, macrophages, Schwann cells, T cells, natural killer cells, and B cells. In comparison with the young group, the aortic wall tissue of the old group showed significant reduction in the proportion of endothelial cells (young vs. old, 22.47% vs. 10.37%), smooth muscle cells (20.40% vs. 18.50%), fibroblasts (30.21% vs. 13.29%), and mesenchymal cells (5.12% vs 1.55%) and significant increase in the proportion of macrophages (10.94% vs. 17.02%) and T cells (3.80% vs. 26.01%). Functional enrichment analysis of the ligand-receptor pairs between the macrophages and the T cells demonstrated enrichment of pathways related to inflammation and endocrine resistance in the elderly group. Immunohistochemical analysis of the aortic tissue from the 58-year-old donor showed higher expression of the M2 macrophage marker, CD163, in comparison with the aortic tissue of the 12-year-old donor. This confirmed the results of the single-cell sequencing analysis. In summary, single-cell sequencing analysis of the normal ascending aorta tissues from multiple donors of different ages demonstrated significant age-related changes in the proportions of multiple cell types, cellular phenotypes, and cell-cell communications. These age-related changes are likely involved in the pathogenesis of age-related aortic diseases.

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Epigenome analysis of aging muscle progenitors

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