Epitranscriptomic modifications are pivotal in RNA metabolism and can exert post-transcriptional influence on gene expression. Recent advances in Next-Generation Sequencing (NGS) have significantly enhanced the detection and mapping of RNA chemical modification sites, expanding the understanding of epitranscriptomics. Governed by these precise modifications, target RNAs undergo diverse fates, contingent on their temporal and spatial context. The most prevalent mRNA modification in eukaryotic cells is adenine methylation at the N6 position (m6A), which plays essential roles in various physiological processes, including embryogenesis, carcinogenesis, and neurogenesis.

Recent studies conducted in experimental models have raised the possibility of RNA methylation (m6A) playing a role in chronic liver disease including MASLD/MASH. The overarching aim of this project is to ascertain the epitranscriptomic profile associated with the presence of MASLD and MASH. Additionally, we aim to pinpoint epitranscriptomic modifications in liquid biopsy samples with diagnostic potential and assess whether modulating epitranscriptomic mechanisms could be a therapeutic avenue for the treatment of MASH by using human liver organoids derived from liver tissue samples of patients with obesity and MASLD.