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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: | Cerdá-Esteban, N., Naumann, H., Ruzittu, S., Mah, N., Pongrac, I.M., Cozzitorto, C., Hommel, A., Andrade-Navarro, M.A., 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. |
| Keywords: | Cell Differentiation, Cell Lineage, Cellular Reprogramming, Cultured Cells, Developmental Gene Expression Regulation, Gene Expression Profiling, Hepatocytes, Homeodomain Proteins, Inbred C57BL Mice, Knockout Mice, Liver, Pancreas, Repressor Proteins, Stem Cells, Transgenic Mice, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| 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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