Loss of Fbw7 Reprograms Adult Pancreatic Ductal Cells into α, δ, and β Cells

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2014 Aug 9

PMID 25105579

Citations 72

Authors

Rocio Sancho

Ralph Gruber

Guoqiang Gu

Axel Behrens

Affiliations

Soon will be listed here.

Abstract

The adult pancreas is capable of limited regeneration after injury but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here, we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into α, δ, and β cells. Loss of Fbw7 stabilized the transcription factor Ngn3, a key regulator of endocrine cell differentiation. The induced β cells resemble islet β cells in morphology and histology, express genes essential for β cell function, and release insulin after glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type.

Citing Articles

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