Myc is required for adaptive beta cell replication in young mice but is not sufficient in one year old mice fed with a high fat

Purpose: To test the role of Myc in adaptive expansion of beta cells Methods: Islets were isolated from 8 week old or one year old male C57BL6 mice fed a standard or high fat diet. RNAseq and DNA mehtylseq was performed. Results: RNAseq showed that Myc target genes are upregulted in young, but not old mice after a short term high fat diet. DNA methylation analysis shows hypomethylation of cell cycle genes that are Myc targets in islets from young mice fed with a HFD. Importantly, DNA hypomethylation of Myc response elements does not occur in islets from one-year-old mice fed short-term HFD Conclusions: We conclude that Myc is required for metabolic stress-mediated beta cell expansion in young mice, but with aging Myc upregulation in beta cells is not sufficient to induce beta cell replication by, at least partly, an epigenetically-mediated resistance to Myc action. RNASeq and MethylSeq of selected genomic regions from islets isolated from 8 week old or 1 year old mice fed a standard or high fat diet. All groups in triplicate or quadruplicate.