Different developmental histories of beta-cells generate functional and proliferative heterogeneity during islet growth

Sumeet Pal Singh, Sharan Janjuha, Theresa Hartmann, Özge Kayisoglu, Judith Konantz, Sarah Birke, Priyanka Murawala, Ezzaldin Ahmed Alfar, Kei Murata, Anne Eugster, Naoki Tsuji, Edward R. Morrissey, Michael Brand and Nikolay Ninov ()
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Sumeet Pal Singh: Technische Universität Dresden
Sharan Janjuha: Technische Universität Dresden
Theresa Hartmann: Technische Universität Dresden
Özge Kayisoglu: Technische Universität Dresden
Judith Konantz: Technische Universität Dresden
Sarah Birke: Technische Universität Dresden
Priyanka Murawala: Technische Universität Dresden
Ezzaldin Ahmed Alfar: Technische Universität Dresden
Kei Murata: Technische Universität Dresden
Anne Eugster: Technische Universität Dresden
Naoki Tsuji: Pain & Neuroscience Lab, Daiichi Sankyo Co., Ltd.
Edward R. Morrissey: Weatherall Institute of Molecular Medicine
Michael Brand: Technische Universität Dresden
Nikolay Ninov: Technische Universität Dresden

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00461-3

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