While numerous studies have uncovered the molecular mechanisms regulating pancreas development, it remains to be clarified how β cells arise from progenitors, and how recently specified β cells are different from pre-existing β cells. To address these questions, we developed a mouse model in which the insulin 1 promoter drives DsRed-E5 “Timer” fluorescence that shifts its spectrum over time. In the transgenic embryos, green-fluorescent β-cells were readily detected by FACS and could be distinguished from mature β cells only until postnatal day 0, suggesting that β cell neogenesis occurs exclusively during embryogenesis. Transcriptome analysis with green-fluorescent cells sorted by FACS demonstrated that newly differentiated β cells highly expressed progenitor markers, such as Sox9, Neurog3, and Pax4, showing the progenitor-like features of newborn β cells. Flow cytometric analysis of cell cycle dynamics showed that green-fluorescent cells were mostly quiescent, and differentiated β cells were mitotically active. Thus, the precise temporal resolution of this model enables us to dissect the unique features of newly specified insulin-producing cells, which could enhance our understanding of β cell neogenesis for future cell therapy.
- Received August 25, 2013.
- Accepted May 6, 2014.
- © 2014 by the American Diabetes Association.
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