RNA-seq analysis in residual pancreatic β-cells of Bmal1KO/DTA mice following massive ablation
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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We aimed to fill the gap in understanding functional roles of the islet cellular oscillators under diabetic conditions following massive β-cell ablation, and during β-cell regeneration. We assessed diurnal regulation of β-cell proliferation and transcriptional landscape in separated α- and residual β-cells -utilizing rtTA/TET-DTA mouse model that bears α- and β-cell specific labeling. Acute hyperglycemia and loss of β-cell mass perturbed absolute expression levels and temporal transcriptome profiles in residual β-cells, whereas in neighboring α-cells only changes in temporal profiles were observed. Strikingly, compensatory regeneration of β-cells exhibited circadian rhythmicity. In arrhythmic BMAL1 knockout mice, massive β-cell ablation led to aggravated hyperglycemia, hyperglucagonemia and a fatal non-compensated diabetes. No activation of β-cell regeneration via entry into cell-cycle was observed in arrhythmic mice, suggesting essential role of functional circadian clocks in this process.
提供机构：
University of Geneva
创建时间：
2022-02-20
