FSHD2と遺伝子活動についての新しい知見

タイトル: Unlocking the Treatment of FacioscapulohumeralMuscular Dystrophy Type 2: The Bisphenol Connection

概要: BackgroundFacioscapulohumeral muscular dystrophy type 2 (FSHD2) poses a significant challenge within the domain of neuromuscular disorders, marked by a progressive decline in muscle strength accompanied by tissue wasting. FSHD2 results from chromosomal deletions triggering the activation of a dormant gene known as DUX4. While DUX4 typically regulates early embryonic development, its activation in adult muscle cells leads to premature cell death. Despite this understanding, the exact pathology of FSHD2 remains unclear. To date, no effective treatment for FSHD2 exists. MethodWe acquired single-cell RNA sequencing (RNA-Seq) data (GSE143452) from primary myoblasts for FSHD2 from the United States National Institutes of Health (NIH) portal website. Our analysis encompassed a comprehensive examination of differentially expressed genes, alongside associated compounds sourced from the Chemical Entities of Biological Interest (ChEBI) database. Employing rigorous statistical methods, we pinpointed the most prominently upregulated and downregulated genes. Subsequently, we determined the compounds capable of modulating the expression of these top genes, either enhancing or reducing their activity. ResultsBisphenol S (BPS) can upregulate 52 of 100 top downregulated genes in FSHD2 without downregulating any other genes and Bisphenol F (BPF) can upregulate 45 of 100 downregulated genes with downregulating only one other gene. The enrichment analysis of both sets of 52 genes related to BPS and 45 genes corresponding to BPF highlights their significant involvement in various aspects of muscle biology, particularly as pertaining to the function and dysfunction of cardiac and skeletal muscle. ConclusionsLeveraging single-cell RNA-Seq data and computational analysis, we identified key dysregulated genes in FSHD2 and elucidated their modulation by compounds such as BPS and BPF. While effective treatments for FSHD2 remain elusive, our study provides valuable insights into potential therapeutic targets and pathways for further investigation in the pursuit of effective interventions for this debilitating condition. However, more research is needed to understand whether the roles of BPS and F are constructive or destructive.