Pluto Bioinformatics

GSE109671: Genome organisation and chromatin analysis identifies transcriptional downregulation of insulin-like growth factor signalling as a hallmark of ageing in developing B cells

Bulk RNA sequencing

Background Ageing is characterised by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of ageing on B cell development, we have profiled gene expression and chromatin features, including histone modifications and chromosome conformation focused on promoter interactions, globally in murine bone marrow pro-B and pre-B cells. Results Our analysis revealed that the expression levels of most genes are generally preserved in B cell precursors isolated from aged as compared to young mice. Nonetheless, age-specific expression changes are observed at numerous genes and are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions and nuclear compartmentalisation. We identified transcriptional downregulation of components of the insulin-like growth factor signalling pathway, in particular downregulation of Irs1 and upregulation of miR/Let-7 expression, as a signature of the aged phenotype. Remarkably, these expression changes are associated with specific alterations in H3K27me3, suggesting that Polycomb-mediated repression plays a role in precursor B cell ageing. Conclusions Components of the insulin-like growth factor signalling pathways are key targets of epigenetic regulation in ageing in bone marrow B cell precursors. SOURCE: Steven,William,Wingett (steven.wingett@babraham.ac.uk) - Babraham Institute