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Interactions between insulin resistance, epigenetics, and donor sex in control of gene expression in human iPS cell-derived myoblasts

ABSTRACT: About 25% of people within the general population are insulin resistant, increasing the risk for type 2 diabetes (T2D) and metabolic disease. Transcriptomic analysis of iPS cells differentiated into myoblasts (iMyos) from insulin resistant (I-Res) versus insulin sensitive (I-Sen) non-diabetic individuals reveals 306 genes increased and 271 genes decreased in expression in iMyos from insulin resistant donors with differences of 2-folds or more. Over 30 of the genes changed in I-Res iMyos are associated with T2D by SNP polymorphisms and functionally linked to insulin action and control of metabolism. Interestingly, we also identified >1500 differences in gene expression that were dependent on sex of the cell donor, some of which modified the insulin resistance effects. Many of these sex-differences were associated with increased DNA methylation in cells from females and reversed by 5-azacytidine. By contrast, the insulin sensitivity differences were not reversed and thus appear to reflect genetic or methylation-independent epigenetic effects.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244307 | GEO | 2024/01/17

REPOSITORIES: GEO

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