Journal
CELL STEM CELL
Volume 15, Issue 2, Pages 139-153Publisher
CELL PRESS
DOI: 10.1016/j.stem.2014.06.019
Keywords
-
Categories
Funding
- Marie Curie grant [MEIF-CT-2006-041119]
- MRC [G0901677]
- ERC [281661]
- EMBO long-term fellowship
- Cancer Research UK
- European Research Council (ERC) [281661] Funding Source: European Research Council (ERC)
- Cancer Research UK [15679] Funding Source: researchfish
- Medical Research Council [G0901677] Funding Source: researchfish
- MRC [G0901677] Funding Source: UKRI
Ask authors/readers for more resources
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 alpha, delta, and beta cells. Loss of Fbw7 stabilized the transcription factor Ngn3, a key regulator of endocrine cell differentiation. The induced beta cells resemble islet beta cells in morphology and histology, express genes essential for beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available