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Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2

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Item Type:Article
Title:Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2
Creators Name:Cerda-Esteban, N. and Naumann, H. and Ruzittu, S. and Mah, N. and Pongrac, I.M. and Cozzitorto, C. and Hommel, A. and Andrade-Navarro, M.A. and Bonifacio, E. and Spagnoli, F.M.
Abstract:The development of a successful lineage reprogramming strategy of liver to pancreas holds promises for the treatment and potential cure of diabetes. The liver is an ideal tissue source for generating pancreatic cells, because of its close developmental origin with the pancreas and its regenerative ability. Yet, the molecular bases of hepatic and pancreatic cellular plasticity are still poorly understood. Here, we report that the TALE homeoprotein TGIF2 acts as a developmental regulator of the pancreas versus liver fate decision and is sufficient to elicit liver-to-pancreas fate conversion both ex vivo and in vivo. Hepatocytes expressing Tgif2 undergo extensive transcriptional remodelling, which represses the original hepatic identity and, over time, induces a pancreatic progenitor-like phenotype. Consistently, in vivo forced expression of Tgif2 activates pancreatic progenitor genes in adult mouse hepatocytes. This study uncovers the reprogramming activity of TGIF2 and suggests a stepwise reprogramming paradigm, whereby a 'lineage-restricted' dedifferentiation step precedes the identity switch.
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:8
Page Range:14127
Date:13 February 2017
Official Publication:https://doi.org/10.1038/ncomms14127
PubMed:View item in PubMed

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