Pluto Bioinformatics

GSE152751: Circadian clocks drive regeneration of pancreatic -cells in mice

Bulk RNA sequencing

We aimed to understand the functional roles of islet cellular oscillators under diabetic conditions and during -cell regeneration. We assessed diurnal regulation of -cell proliferation and the transcriptional landscape in - and residual -cells following -cell ablation in Insulin-rtTA/TET-DTA mice that simultaneously expressed - and -cell specific fluorescent reports. The mouse pancreatic islets were isolated over 24-h with 4-h interval, followed by separation of - and - cells using FACS sorting, RNA extraction and RNA sequencing. 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 deficient mice, massive -cell ablation led to aggravated hyperglycemia, hyperglucagonemia and a fatal diabetes. No compensatory proliferation of -cells was observed in arrhythmic mice, suggesting an essential role of circadian clocks in -cell regeneration. SOURCE: Cedric Howald (cedric.howald@health2030.ch) - Health2030 Genome Center

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