B2 -The miRNA and single cell perspectives of the E2F1/inflammation/autophagy network in human adipose tissue

Autophagy plays an important role in the development of adipose tissue dysfunction. In human obesity, activation of autophagy is regulated by E2F1 and specific miRNAs. The project now takes the E2F1-autophagy/inflammation network to the single-cell level. Single-nucleus RNA-sequencing (sNucSeq) will be used to capture the cellular repertoire and the single cell-type impact of the E2F1 network. The project further aims to understand how E2F1 signifies changes in the repertoire of adipose tissue miRNAs and to what degree these are reflected in circulating miRNAs. Finally, it will be determined if these E2F1 network components constitute biomarkers to predict clinical outcomes in response to bariatric surgery, such as weight loss, metabolic improvement, diabetes remission, and a decrease in cardiovascular risk parameters.

Figure 1. Increased human AT E2F1 expression and E2F1 mRNA stability. A. Hierarchical clustering of differentially expressed genes. Differential trans­criptome between E2F1^high and E2F1^low is presented, divided to clusters of upregulated and downregulated genes. B and C. Selected pathway analyses, using STRING₁₀© protein-interaction database. Shown are predicted and/or experimentally established pathways of ECM-related genes and TNF-related superfamily genes, differentially expressed in our cohort. Line thickness represents confidence level of the interaction.

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