Heterogeneity of gene expression and rarity of replication hamper molecular analysis of β-cell mass restoration in adult pancreas. Here, we show transcriptional dynamics in β-cell replication process by single-cell RNA sequencing of murine pancreas with or without partial pancreatectomy. We observed heterogeneity of Ins1-expressing β-cells and identified the one cluster as replicating β-cells with high expression of cell proliferation markers Pcna and Mki67. We also recapitulated cell cycle transition accompanied with switching expression of cyclins and E2F transcription factors. Both transient activation of endoplasmic reticulum stress responders like Atf6 and Hspa5 and elevated expression of tumor suppressors like Trp53, Rb1, and Brca1 and DNA damage responders like Atm, Atr, Rad51, Chek1, and Chek2 during the transition to replication associated fine balance of cell cycle progression and protection from DNA damage. Taken together, these results provide a high-resolution map depicting a sophisticated genetic circuit for replication of the β-cells.

基因表达的异质性和复制的稀有性阻碍了成年胰腺β细胞大规模恢复的分子分析。在这里，我们通过有或没有部分胰腺切除术的小鼠胰腺的单细胞RNA测序显示了β细胞复制过程中的转录动力学。我们观察到表达Ins1的β细胞的异质性，并鉴定出一个簇是具有高表达细胞增殖标志物Pcna和Mki67的复制性β细胞。我们还概括了细胞周期过渡，伴随着细胞周期蛋白和E2F转录因子的开关表达。内质网应激反应物如Atf6和Hspa5的瞬时激活Trp53，Rb1和Brca1等肿瘤抑制因子的表达升高，以及Atm，Atr，Rad51，Chek1和Chek2等DNA损伤响应因子在复制过程中的转化与细胞周期进程的精细平衡和DNA损伤的保护相关。综上所述，这些结果提供了高分辨率图，其描绘了用于复制β细胞的复杂遗传电路。