Tatsuoka Hisato, Sakamoto Satoko, Yabe Daisuke, Kabai Ryotaro, Kato Unyanee, Okumura Tatsuya, Botagarova Ainur, Tokumoto Shinsuke, Usui Ryota, Ogura Masahito, Nagashima Kazuaki, Mukai Eri, Fujitani Yoshio, Watanabe Akira, Inagaki Nobuya
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
iScience. 2020 Nov 6;23(12):101774. doi: 10.1016/j.isci.2020.101774. eCollection 2020 Dec 18.
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 -expressing β-cells and identified the one cluster as replicating β-cells with high expression of cell proliferation markers and . We also recapitulated cell cycle transition accompanied with switching expression of and E2F transcription factors. Both transient activation of endoplasmic reticulum stress responders like and and elevated expression of tumor suppressors like , , and DNA damage responders like , , , , and 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对成年胰腺中β细胞质量恢复的分子分析。在此，我们通过对有或无部分胰腺切除术的小鼠胰腺进行单细胞RNA测序，展示了β细胞复制过程中的转录动态。我们观察到表达β细胞的异质性，并将一个簇鉴定为具有高细胞增殖标志物表达的复制β细胞。我们还概括了伴随着和E2F转录因子表达切换的细胞周期转变。在内质网应激反应者如和的瞬时激活以及肿瘤抑制因子如、、和DNA损伤反应者如、、、、和在向复制转变期间的表达升高与细胞周期进程的精细平衡以及免受DNA损伤有关。综上所述，这些结果提供了一个高分辨率图谱，描绘了β细胞复制的复杂遗传回路。
