Open Access Green as soon as Postprint is submitted to ZB.
Different levels of Notch signaling regulate quiescence, renewal and differentiation in pancreatic endocrine progenitors.
Development 139, 1557-1567 (2012)
Genetic studies have implicated Notch signaling in the maintenance of pancreatic progenitors. However, how Notch signaling regulates the quiescent, proliferative or differentiation behaviors of pancreatic progenitors at the single-cell level remains unclear. Here, using single-cell genetic analyses and a new transgenic system that allows dynamic assessment of Notch signaling, we address how discrete levels of Notch signaling regulate the behavior of endocrine progenitors in the zebrafish intrapancreatic duct. We find that these progenitors experience different levels of Notch signaling, which in turn regulate distinct cellular outcomes. High levels of Notch signaling induce quiescence, whereas lower levels promote progenitor amplification. The sustained downregulation of Notch signaling triggers a multistep process that includes cell cycle entry and progenitor amplification prior to endocrine differentiation. Importantly, progenitor amplification and differentiation can be uncoupled by modulating the duration and/or extent of Notch signaling downregulation, indicating that these processes are triggered by distinct levels of Notch signaling. These data show that different levels of Notch signaling drive distinct behaviors in a progenitor population.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0950-1991
Quellenangaben Volume: 139, Issue: 9, Pages: 1557-1567
Publisher Company of Biologists
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)