Cell cycle-dependent differentiation dynamics balances growth and endocrine differentiation in the pancreas

PLoS Biology
Yung Hae KimAnne Grapin-Botton

Abstract

Organogenesis relies on the spatiotemporal balancing of differentiation and proliferation driven by an expanding pool of progenitor cells. In the mouse pancreas, lineage tracing at the population level has shown that the expanding pancreas progenitors can initially give rise to all endocrine, ductal, and acinar cells but become bipotent by embryonic day 13.5, giving rise to endocrine cells and ductal cells. However, the dynamics of individual progenitors balancing self-renewal and lineage-specific differentiation has never been described. Using three-dimensional live imaging and in vivo clonal analysis, we reveal the contribution of individual cells to the global behaviour and demonstrate three modes of progenitor divisions: symmetric renewing, symmetric endocrinogenic, and asymmetric generating a progenitor and an endocrine progenitor. Quantitative analysis shows that the endocrine differentiation process is consistent with a simple model of cell cycle-dependent stochastic priming of progenitors to endocrine fate. The findings provide insights to define control parameters to optimize the generation of β-cells in vitro.

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Citations

Sep 28, 2015·Trends in Cell Biology·Stephen Dalton
Aug 16, 2017·Development·Aimée Bastidas-PonceMostafa Bakhti
Feb 13, 2021·Frontiers in Cell and Developmental Biology·Jenny OstropMenno J Oudhoff
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May 9, 2021·Biophysical Journal·Abraham Q KohrmanEszter Posfai

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Datasets Mentioned

BETA
AAH25189
AAI04328.1

Methods Mentioned

BETA
transgenic
Fluorescence
Flow cytometry

Software Mentioned

NEUROG3
Fiji
Leica AF6000
Imaris
GraphPad Prism

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