Pluto Bioinformatics

GSE151338: RNA-seq analysis in residual pancreatic -cells of Bmal1KO/DTA mice following massive ablation

Bulk RNA sequencing

We aimed to fill the gap in understanding functional roles of the islet cellular oscillators under diabetic conditions following massive -cell ablation, and during -cell regeneration. We assessed diurnal regulation of -cell proliferation and transcriptional landscape in separated - and residual -cells -utilizing rtTA/TET-DTA mouse model that bears - and -cell specific labeling. Acute hyperglycemia and loss of -cell mass perturbed absolute expression levels and temporal transcriptome profiles in residual -cells, whereas in neighboring -cells only changes in temporal profiles were observed. Strikingly, compensatory regeneration of -cells exhibited circadian rhythmicity. In arrhythmic BMAL1 knockout mice, massive -cell ablation led to aggravated hyperglycemia, hyperglucagonemia and a fatal non-compensated diabetes. No activation of -cell regeneration via entry into cell-cycle was observed in arrhythmic mice, suggesting essential role of functional circadian clocks in this process. SOURCE: Celine Delucinge University of Geneva