Chronological Analysis With Fluorescent Timer Reveals Unique Features of Newly Generated b-Cells

Although numerous studies have uncovered the molec-ular mechanisms regulating pancreas development, it remains to be clarified how b-cells arise from progenitors and how recently specified b-cells are different from pre-existing b-cells. To address these questions, we devel-oped a mouse model in which the insulin 1 promoter drives DsRed-E5 Timer fluorescence that shifts its spec-trum over time. In transgenic embryos, green fluorescent b-cells were readily detected by FACS and could be dis-tinguished from mature b-cells only until postnatal day 0, suggesting that b-cell neogenesis occurs exclusively dur-ing embryogenesis. Transcriptome analysis with green fluorescent cells sorted by FACS demonstrated that newly differentiated b-cells highly expressed progenitor markers, such as Sox9, Neurog3, and Pax4, showing th