Islet single-cell transcriptomic profiling during obesity-induced beta cell expansion

Transcriptional mechanisms of beta cell proliferation are incompletely understood. We used single-cell transcriptomics to identify gene networks and signaling pathways central to beta cell proliferation Islets were isolated from control (wild-type; Lepr-lp/lp) and Lepr KO (Ubc-CreERT2;Lepr-lp/lp) mice on day 9 after the start of tamoxifen treatment, which was used to induce Cre-recombination at the Lepr leading to hyperphagia, weight gain, and beta cell mass expansion.

胰岛β细胞增殖的转录调控机制目前尚未完全阐明。本研究采用单细胞转录组学（single-cell transcriptomics）技术，筛选调控β细胞增殖的核心基因网络与信号通路。实验所用小鼠分为两组：对照组为野生型（wild-type）Lepr-lp/lp小鼠，Lepr敲除（Lepr KO）组为Ubc-CreERT2;Lepr-lp/lp基因型小鼠；在他莫昔芬（tamoxifen）给药启动后的第9天，我们分离两组小鼠的胰岛。他莫昔芬可诱导Lepr位点发生Cre重组酶介导的重组（Cre-recombination），进而引发小鼠食欲亢进、体重增加以及胰岛β细胞团块扩增。