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Diabetes. 2014 Oct;63(10):3388-93. doi: 10.2337/db13-1312. Epub 2014 May 16.

Chronological analysis with fluorescent timer reveals unique features of newly generated β-cells.

Author information

  • 1Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, Tokyo, Japan Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan miyatsuka-takeshi@umin.net.
  • 2Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
  • 3Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 4Diabetes Center, University of California San Francisco, San Francisco, CA.
  • 5Department of Medicine, The University of Chicago, Chicago, IL.

Abstract

Although 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 preexisting 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 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.

© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PMID:
24834978
[PubMed - indexed for MEDLINE]
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