Chu Chieh Min, Sabbineni Bhavya, Cen Haoning Howard, Hu Xiaoke, Sun WenQing Grace, Brownrigg George P, Xia Yi Han, Rogalski Jason, Johnson James D
Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia and the Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.
Proteomics and Metabolomics Core Facility, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
iScience. 2025 Feb 17;28(3):112015. doi: 10.1016/j.isci.2025.112015. eCollection 2025 Mar 21.
Pancreatic β cells exist in low and high insulin gene activity states that are dynamic on a scale of hours to days. Here, we used live 3D imaging, mass spectrometry proteomics, and targeted perturbations of β cell signaling to comprehensively investigate (GFP) and (GFP) β cell states. We identified the two gene activity states in intact isolated islets and showed that cells in the same state were more likely to be nearer to each other. We report the proteomes of pure β cells to a depth of 5555 proteins and show that β cells with high gene activity had reduced β cell immaturity factors, as well as increased translation. We identified activators of cAMP signaling (GLP1, IBMX) as powerful drivers of (GFP) to (GFP) transitions. Okadaic acid and cyclosporine A had the opposite effects. This study provides new insight into the proteomic profiles and regulation of β cell states.
胰腺β细胞存在低胰岛素基因活性状态和高胰岛素基因活性状态，这些状态在数小时至数天的时间尺度上是动态变化的。在这里，我们使用实时3D成像、质谱蛋白质组学以及对β细胞信号传导的靶向扰动，全面研究绿色荧光蛋白（GFP）和绿色荧光蛋白（GFP）β细胞状态。我们在完整分离的胰岛中鉴定出两种基因活性状态，并表明处于相同状态的细胞彼此更有可能靠得更近。我们报告了深度达5555种蛋白质的纯β细胞蛋白质组，并表明具有高基因活性的β细胞具有减少的β细胞不成熟因子以及增加的翻译。我们确定环磷酸腺苷（cAMP）信号传导的激活剂（胰高血糖素样肽1、异丁基甲基黄嘌呤）是绿色荧光蛋白（GFP）向绿色荧光蛋白（GFP）转变的强大驱动因素。冈田酸和环孢素A则具有相反的作用。这项研究为β细胞状态的蛋白质组学特征和调控提供了新的见解。
