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

Glucagon-expressing pancreatic a cells have attracted much attention for their plasticity to transdifferentiate into insulin-producing ß cells; however, it remains unclear precisely when and where a cells emerge from and what regulates a-cell fate. We therefore explored the spatial and transcriptional heterogeneity of a-cell differentiation by a novel time-resolved reporter system. We established the mouse model, 'Gcg-Timer', in which newly generated a 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-a cells. Novel time-resolved analysis with Gcg-Timer reporter mouse uncovered spatiotemporal features of a-cell neogenesis, which will enhance our understanding of cellular identity and plasticity within the islets. Overall design: This study characterizes the transcriptomes of mouse pancreatic a-lineage cells. Pancreas from Gcg-Timer at E17.5 were dissociated and sorted by FACS into 3 groups (N: non-a cell, A: green dominant_newly generated-a cell, and B: green and red_more differentiated-a cell). 4 replicate data were colleced from different mother mice. RNA were extracted and RNA sequencing was performed.