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

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.Βeta-cells have recently been shown to be heterogeneous with regard to morphology and function. Here, the authors show that β-cells in zebrafish switch from proliferative to functional states with increasing time since β-cell birth, leading to functional and proliferative heterogeneity.

journal_name

Nat Commun

journal_title

Nature communications

authors

Singh SP,Janjuha S,Hartmann T,Kayisoglu Ö,Konantz J,Birke S,Murawala P,Alfar EA,Murata K,Eugster A,Tsuji N,Morrissey ER,Brand M,Ninov N

doi

10.1038/s41467-017-00461-3

subject

Has Abstract

pub_date

2017-09-22 00:00:00

pages

664

issue

1

issn

2041-1723

pii

10.1038/s41467-017-00461-3

journal_volume

8

pub_type

杂志文章

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