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FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1

Fibroblast growth factors (FGFs) are required to specify hepatic fate within the definitive endoderm through activation of the FGF receptors (FGFRs). While the signaling pathways involved in hepatic specification are well understood, the mechanisms through which FGFs induce hepatic character within...

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Autores principales: Twaroski, Kirk, Mallanna, Sunil K., Jing, Ran, DiFurio, Francesca, Urick, Amanda, Duncan, Stephen A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691950/
https://www.ncbi.nlm.nih.gov/pubmed/26637527
http://dx.doi.org/10.1101/gad.268961.115
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author Twaroski, Kirk
Mallanna, Sunil K.
Jing, Ran
DiFurio, Francesca
Urick, Amanda
Duncan, Stephen A.
author_facet Twaroski, Kirk
Mallanna, Sunil K.
Jing, Ran
DiFurio, Francesca
Urick, Amanda
Duncan, Stephen A.
author_sort Twaroski, Kirk
collection PubMed
description Fibroblast growth factors (FGFs) are required to specify hepatic fate within the definitive endoderm through activation of the FGF receptors (FGFRs). While the signaling pathways involved in hepatic specification are well understood, the mechanisms through which FGFs induce hepatic character within the endoderm are ill defined. Here we report the identification of genes whose expression is directly regulated by FGFR activity during the transition from endoderm to hepatic progenitor cell. The FGFR immediate early genes that were identified include those encoding transcription factors, growth factors, and signaling molecules. One of these immediate early genes encodes naked cuticle homolog 1 (NKD1), which is a repressor of canonical WNT (wingless-type MMTV integration site) signaling. We show that loss of NKD1 suppresses the formation of hepatic progenitor cells from human induced pluripotent stem cells and that this phenotype can be rescued by using a pharmacological antagonist of canonical WNT signaling. We conclude that FGF specifies hepatic fate at least in large part by inducing expression of NKD1 to transiently suppress the canonical WNT pathway.
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spelling pubmed-46919502016-06-01 FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1 Twaroski, Kirk Mallanna, Sunil K. Jing, Ran DiFurio, Francesca Urick, Amanda Duncan, Stephen A. Genes Dev Research Paper Fibroblast growth factors (FGFs) are required to specify hepatic fate within the definitive endoderm through activation of the FGF receptors (FGFRs). While the signaling pathways involved in hepatic specification are well understood, the mechanisms through which FGFs induce hepatic character within the endoderm are ill defined. Here we report the identification of genes whose expression is directly regulated by FGFR activity during the transition from endoderm to hepatic progenitor cell. The FGFR immediate early genes that were identified include those encoding transcription factors, growth factors, and signaling molecules. One of these immediate early genes encodes naked cuticle homolog 1 (NKD1), which is a repressor of canonical WNT (wingless-type MMTV integration site) signaling. We show that loss of NKD1 suppresses the formation of hepatic progenitor cells from human induced pluripotent stem cells and that this phenotype can be rescued by using a pharmacological antagonist of canonical WNT signaling. We conclude that FGF specifies hepatic fate at least in large part by inducing expression of NKD1 to transiently suppress the canonical WNT pathway. Cold Spring Harbor Laboratory Press 2015-12-01 /pmc/articles/PMC4691950/ /pubmed/26637527 http://dx.doi.org/10.1101/gad.268961.115 Text en © 2015 Twaroski et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Twaroski, Kirk
Mallanna, Sunil K.
Jing, Ran
DiFurio, Francesca
Urick, Amanda
Duncan, Stephen A.
FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1
title FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1
title_full FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1
title_fullStr FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1
title_full_unstemmed FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1
title_short FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1
title_sort fgf2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the wnt antagonist nkd1
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691950/
https://www.ncbi.nlm.nih.gov/pubmed/26637527
http://dx.doi.org/10.1101/gad.268961.115
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