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oai:figshare.com:article/33828133 2026-09-16T04:37:43Z category_658 portal_316 item_type_3 month_year_09_2026

Table 4_Integrative multi-omics analysis unveils the regulatory landscape of diabetic cardiomyopathy: from chromatin accessibility to transcript isoforms and epitranscriptome.xlsx Licheng Ding (15350323) Kaiyuan Liu (6703433) Xiaofeng Ge (24960598) Zhaokai Li (22435285) Ke Hu (84619) Shichen Bu (19218136) Cell Metabolism diabetic cardiomyopathy epitranscriptomics Fam210b multi-omics integration T-cell infiltration <p>Diabetic cardiomyopathy (DCM) is a major contributor to heart failure in diabetic patients, characterized by profound metabolic remodeling and diastolic dysfunction. However, the multi-layered epitranscriptomic and post-transcriptional networks involved in this disease remain poorly understood. To address this, we established a type 2 diabetes-associated DCM mouse model using a high-fat diet (HFD) combined with low-dose streptozotocin (STZ) injections. By integrating single-molecule direct RNA sequencing (DRS-seq), chromatin accessibility profiling (ATAC-seq), and conventional bulk RNA-seq, we constructed a comprehensive epigenetic-transcriptional regulatory map of DCM. Using DRS-seq, we identified 21,156 full-length transcripts, including 8,457 (39.97%) novel unannotated isoforms, and observed a systemic 3’-UTR elongation under diabetic stress. Joint ATAC-seq and DRS-seq analysis identified concurrent reductions in promoter chromatin accessibility and transcript abundance for four genes, including Fam210b (mitochondrial iron homeostasis), Cdh22 (intercalated disc adhesion), Fbxo10 (ubiquitin-mediated RAGE degradation), and Cenpx (DNA double-strand break repair), suggesting a potential link between altered chromatin accessibility and transcriptional regulation in DCM. 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> 2026-09-16T04:37:43Z Dataset Dataset 10.3389/fendo.2026.1928778.s001 https://figshare.com/articles/dataset/Table_4_Integrative_multi-omics_analysis_unveils_the_regulatory_landscape_of_diabetic_cardiomyopathy_from_chromatin_accessibility_to_transcript_isoforms_and_epitranscriptome_xlsx/33828133 CC BY 4.0