Single-Cell Transcriptome Analysis Dissects the Replicating Process of Pancreatic Beta Cells in Partial Pancreatectomy Model

• Published in: iScience Vol. 23; no. 12; p. 101774
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 18-12-2020; Elsevier
• Subjects: Biological Sciences; Genomics; Molecular Biology; Molecular Biology; Biological Sciences; Genomics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.101774

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.
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•Single cell RNA sequencing dissects a sequence of replication process of beta cells•ER stress responders are transiently activated in initiation of the proliferation•Physiological replication accompanied with induced expression of tumor suppressors•Fine balance of proliferation genes and tumor suppressors is a key of the replication
Biological Sciences; Molecular Biology; Genomics