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

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.