Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells.

Sancho R, Gruber R, Gu G, Behrens A
Cell Stem Cell. 2014 15 (2): 139-53

PMID: 25105579 · PMCID: PMC4136739 · DOI:10.1016/j.stem.2014.06.019

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.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

MeSH Terms (26)

Animals Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Cell Line, Tumor Cell Lineage F-Box-WD Repeat-Containing Protein 7 F-Box Proteins Gene Deletion Gene Expression Profiling Gene Expression Regulation, Developmental Glucagon-Secreting Cells Glucose HEK293 Cells Humans Insulin Insulin-Secreting Cells Insulin Secretion Mice Multipotent Stem Cells Nerve Tissue Proteins Pancreatic Ducts Proteasome Endopeptidase Complex Regeneration Somatostatin-Secreting Cells Ubiquitin-Protein Ligases Ubiquitination

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