摘要：SummaryHeterogeneity 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 ofIns1-expressing β-cells and identified the one cluster as replicating β-cells with high expression of cell proliferation markersPcnaandMki67. We also recapitulated cell cycle transition accompanied with switching expression ofcyclinsand E2F transcription factors. Both transient activation of endoplasmic reticulum stress responders likeAtf6andHspa5and elevated expression of tumor suppressors likeTrp53,Rb1,and Brca1and DNA damage responders likeAtm,Atr,Rad51,Chek1, andChek2during 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.Graphical AbstractDisplay OmittedHighlights•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 replicationBiological Sciences; Molecular Biology; Genomics
