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microRNAs confer robustness to adult beta–cell identity

Final Report Summary - MIRNABETAIDENTITY (microRNAs confer robustness to adult beta–cell identity)

Hornstein lab ERC project was focused on non coding RNA function in tissue biology and maintenance of cellular identity by endogenous and non-coding microRNAs. The project has moved the Hornstein lab in developing new molecular technologies for molecular medicine cellular and tissue biology.
The technical achievements beyond state of the art include (1) several mouse transgene and knock in lines that assist research of human disease and are available for the scientific community (2) a platform for interrogation of subcellular compartments with focus on RNA-RNA-binding protein condensates, whereby RNA regulatory activity takes place (3) adapting single cell sequencing for characterization of cellular heterogeneity in the regenerating endocrine pancreas and (4) a sensitive quantification techniques that can measure miRNA in biofluids.
The scientific breakthroughs beyond state of the art include (1) the revelation that miRNA assist in maintenance of cellular fate, (2) miRNA safeguard against the activity of alternative and disallowed genetic programs that could derail cells from normal function. (3) miRNA control pathways that are involved in human disease and pathways controlled by clinal drugs, suggesting that certain therapeutic effects are mediated via miRNAs and that miRNA themselves can be targets for future interventions. (4) In addition, an emerging concept from our research is that miRNAs can re-shape the transcriptome of cells in such a way the morph house keeping genetic programs that are active in all types of cells into a boutique version, tailored for the specific needs of specialized cells.