Table 2_Integrative multi-omics analysis unveils the regulatory landscape of diabetic cardiomyopathy: from chromatin accessibility to transcript isoforms and epitranscriptome.xls

Additionally, DRS-seq revealed extensive alterations in the cardiac epitranscriptome, identifying 1,719 differential m⁶A sites and 3,146 differential m⁵C sites at single-molecule resolution. Among these epitranscriptomic changes, we observed a potential post-transcriptional interplay between m⁶A and alternative polyadenylation (APA). Furthermore, by applying the CIBERSORT algorithm to the DRS-seq dataset, we characterized the cardiac immune microenvironment, revealing distinct pathological remodeling defined by decreased plasma cells and Th1 cells alongside a specific increase in CD4+ memory T-cell infiltration.

Pearson correlation analysis showed that, among the candidate genes, only the down-regulated mitochondrial regulator Fam210b exhibited a significant negative correlation with CD4+ memory T-cell infiltration, suggesting a potential molecular association between mitochondrial dysfunction and local adaptive immune changes. Together, our study provides a high-resolution landscape of the native cardiac transcriptome and epitranscriptome, highlighting epigenetic-transcriptional coupling, m⁶A-APA cooperative decay, and Fam210b-associated local immune microenvironment remodeling as potential pathogenic contributor, thus offering candidate therapeutic targets for diabetic heart failure.</p>