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- Title
Different developmental histories of beta-cells generate functional and proliferative heterogeneity during islet growth.
- Authors
Singh, Sumeet Pal; Janjuha, Sharan; Hartmann, Theresa; Kayisoglu, Özge; Konantz, Judith; Birke, Sarah; Murawala, Priyanka; Alfar, Ezzaldin Ahmed; Kei Murata; Eugster, Anne; Naoki Tsuji; Morrissey, Edward R.; Brand, Michael; Ninov, Nikolay
- Abstract
The proliferative and functional heterogeneity among seemingly uniform cells is a universal phenomenon. Identifying the underlying factors requires single-cell analysis of function and proliferation. Here we show that the pancreatic beta-cells in zebrafish exhibit different growth-promoting and functional properties, which in part reflect differences in the time elapsed since birth of the cells. Calcium imaging shows that the beta-cells in the embryonic islet become functional during early zebrafish development. At later stages, younger beta-cells join the islet following differentiation from post-embryonic progenitors. Notably, the older and younger beta-cells occupy different regions within the islet, which generates topological asymmetries in glucose responsiveness and proliferation. Specifically, the older beta-cells exhibit robust glucose responsiveness, whereas younger beta-cells are more proliferative but less functional. As the islet approaches its mature state, heterogeneity diminishes and beta-cells synchronize function and proliferation. Our work illustrates a dynamic model of heterogeneity based on evolving proliferative and functional beta-cell states.
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-00461-3