Novel time-resolved reporter mouse reveals spatial and transcriptional heterogeneity during alpha cell differentiation

Glucagon-expressing pancreatic alpha cells have attracted much attention for their plasticity to transdifferentiate into insulin-producing beta cells; however, it remains unclear precisely when and where alpha cells emerge from and what regulates beta-cell fate. We therefore explored the spatial and transcriptional heterogeneity of alpha-cell differentiation by a novel time-resolved reporter system. We established the mouse model, 'Gcg-Timer', in which newly generated alpha cells can be distinguished from more differentiated cells by their fluorescence. Transcriptome analysis of Gcg-Timer embryos revealed that the mRNAs related to angiogenesis were enriched in newly generated-alpha cells. Novel time-resolved analysis with Gcg-Timer reporter mouse uncovered spatiotemporal features of alpha-cell neogenesis, which will enhance our understanding of cellular identity and plasticity within the islets.