Cargando…

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

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 a...

Descripción completa

Detalles Bibliográficos
Autores principales: Cerdá-Esteban, Nuria, Naumann, Heike, Ruzittu, Silvia, Mah, Nancy, Pongrac, Igor M., Cozzitorto, Corinna, Hommel, Angela, Andrade-Navarro, Miguel A., Bonifacio, Ezio, Spagnoli, Francesca M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316826/
https://www.ncbi.nlm.nih.gov/pubmed/28193997
http://dx.doi.org/10.1038/ncomms14127
_version_ 1782508898059550720
author Cerdá-Esteban, Nuria
Naumann, Heike
Ruzittu, Silvia
Mah, Nancy
Pongrac, Igor M.
Cozzitorto, Corinna
Hommel, Angela
Andrade-Navarro, Miguel A.
Bonifacio, Ezio
Spagnoli, Francesca M.
author_facet Cerdá-Esteban, Nuria
Naumann, Heike
Ruzittu, Silvia
Mah, Nancy
Pongrac, Igor M.
Cozzitorto, Corinna
Hommel, Angela
Andrade-Navarro, Miguel A.
Bonifacio, Ezio
Spagnoli, Francesca M.
author_sort Cerdá-Esteban, Nuria
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5316826
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-53168262017-02-27 Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2 Cerdá-Esteban, Nuria Naumann, Heike Ruzittu, Silvia Mah, Nancy Pongrac, Igor M. Cozzitorto, Corinna Hommel, Angela Andrade-Navarro, Miguel A. Bonifacio, Ezio Spagnoli, Francesca M. Nat Commun Article 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. Nature Publishing Group 2017-02-13 /pmc/articles/PMC5316826/ /pubmed/28193997 http://dx.doi.org/10.1038/ncomms14127 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Cerdá-Esteban, Nuria
Naumann, Heike
Ruzittu, Silvia
Mah, Nancy
Pongrac, Igor M.
Cozzitorto, Corinna
Hommel, Angela
Andrade-Navarro, Miguel A.
Bonifacio, Ezio
Spagnoli, Francesca M.
Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2
title Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2
title_full Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2
title_fullStr Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2
title_full_unstemmed Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2
title_short Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2
title_sort stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator tgif2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316826/
https://www.ncbi.nlm.nih.gov/pubmed/28193997
http://dx.doi.org/10.1038/ncomms14127
work_keys_str_mv AT cerdaestebannuria stepwisereprogrammingoflivercellstoapancreasprogenitorstatebythetranscriptionalregulatortgif2
AT naumannheike stepwisereprogrammingoflivercellstoapancreasprogenitorstatebythetranscriptionalregulatortgif2
AT ruzittusilvia stepwisereprogrammingoflivercellstoapancreasprogenitorstatebythetranscriptionalregulatortgif2
AT mahnancy stepwisereprogrammingoflivercellstoapancreasprogenitorstatebythetranscriptionalregulatortgif2
AT pongracigorm stepwisereprogrammingoflivercellstoapancreasprogenitorstatebythetranscriptionalregulatortgif2
AT cozzitortocorinna stepwisereprogrammingoflivercellstoapancreasprogenitorstatebythetranscriptionalregulatortgif2
AT hommelangela stepwisereprogrammingoflivercellstoapancreasprogenitorstatebythetranscriptionalregulatortgif2
AT andradenavarromiguela stepwisereprogrammingoflivercellstoapancreasprogenitorstatebythetranscriptionalregulatortgif2
AT bonifacioezio stepwisereprogrammingoflivercellstoapancreasprogenitorstatebythetranscriptionalregulatortgif2
AT spagnolifrancescam stepwisereprogrammingoflivercellstoapancreasprogenitorstatebythetranscriptionalregulatortgif2