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- Title
Chronological Analysis With Fluorescent Timer Reveals Unique Features of Newly Generated β-Cells.
- Authors
Takeshi Miyatsuka; Taka-aki Matsuoka; Shugo Sasaki; Fumiyo Kubo; Iichiro Shimomura; Hirotaka Watada; German, Michael S.; Manami Hara
- 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.
- Subjects
DIABETES; PROGENITOR cells; EMBRYOLOGY; TRANSGENIC mice; CELL cycle; INSULIN
- Publication
Diabetes, 2014, Vol 63, Issue 10, p3388
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db13-1312