Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation

The function of pluripotency genes in differentiation is a matter of investigation. We report here that Nanog and Oct4 are reexpressed in two mouse embryonic stem cell (mESC) lines following exposure to the differentiating agent DETA/NO. Both cell lines express a battery of both endoderm and mesoder...

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Main Authors: Sergio Mora-Castilla, Juan R. Tejedo, Rafael Tapia-Limonchi, Irene Díaz, Ana B. Hitos, Gladys M. Cahuana, Abdelkrim Hmadcha, Franz Martín, Bernat Soria, Francisco J. Bedoya
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2014/379678
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author Sergio Mora-Castilla
Juan R. Tejedo
Rafael Tapia-Limonchi
Irene Díaz
Ana B. Hitos
Gladys M. Cahuana
Abdelkrim Hmadcha
Franz Martín
Bernat Soria
Francisco J. Bedoya
author_facet Sergio Mora-Castilla
Juan R. Tejedo
Rafael Tapia-Limonchi
Irene Díaz
Ana B. Hitos
Gladys M. Cahuana
Abdelkrim Hmadcha
Franz Martín
Bernat Soria
Francisco J. Bedoya
author_sort Sergio Mora-Castilla
collection DOAJ
description The function of pluripotency genes in differentiation is a matter of investigation. We report here that Nanog and Oct4 are reexpressed in two mouse embryonic stem cell (mESC) lines following exposure to the differentiating agent DETA/NO. Both cell lines express a battery of both endoderm and mesoderm markers following induction of differentiation with DETA/NO-based protocols. Confocal analysis of cells undergoing directed differentiation shows that the majority of cells expressing Nanog express also endoderm genes such as Gata4 and FoxA2 (75.4% and 96.2%, resp.). Simultaneously, mRNA of mesodermal markers Flk1 and Mef2c are also regulated by the treatment. Acetylated histone H3 occupancy at the promoter of Nanog is involved in the process of reexpression. Furthermore, Nanog binding to the promoter of Brachyury leads to repression of this gene, thus disrupting mesendoderm transition.
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series Stem Cells International
spelling doaj-art-dc37e336d2a740bb86339bfcc9dc686b2025-02-03T06:42:02ZengWileyStem Cells International1687-966X1687-96782014-01-01201410.1155/2014/379678379678Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage DifferentiationSergio Mora-Castilla0Juan R. Tejedo1Rafael Tapia-Limonchi2Irene Díaz3Ana B. Hitos4Gladys M. Cahuana5Abdelkrim Hmadcha6Franz Martín7Bernat Soria8Francisco J. Bedoya9Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University Pablo de Olavide, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red-Tercel, Avenida Américo Vespucio S/N, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University Pablo de Olavide, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red-Tercel, Avenida Américo Vespucio S/N, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University Pablo de Olavide, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red-Tercel, Avenida Américo Vespucio S/N, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University Pablo de Olavide, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red-Tercel, Avenida Américo Vespucio S/N, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University Pablo de Olavide, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red-Tercel, Avenida Américo Vespucio S/N, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University Pablo de Olavide, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red-Tercel, Avenida Américo Vespucio S/N, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Progress and Health Foundation, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red TerCel, Américo Vespucio S/N, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University Pablo de Olavide, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red-Tercel, Avenida Américo Vespucio S/N, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Progress and Health Foundation, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red TerCel, Américo Vespucio S/N, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University Pablo de Olavide, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red-Tercel, Avenida Américo Vespucio S/N, 41092 Seville, SpainThe function of pluripotency genes in differentiation is a matter of investigation. We report here that Nanog and Oct4 are reexpressed in two mouse embryonic stem cell (mESC) lines following exposure to the differentiating agent DETA/NO. Both cell lines express a battery of both endoderm and mesoderm markers following induction of differentiation with DETA/NO-based protocols. Confocal analysis of cells undergoing directed differentiation shows that the majority of cells expressing Nanog express also endoderm genes such as Gata4 and FoxA2 (75.4% and 96.2%, resp.). Simultaneously, mRNA of mesodermal markers Flk1 and Mef2c are also regulated by the treatment. Acetylated histone H3 occupancy at the promoter of Nanog is involved in the process of reexpression. Furthermore, Nanog binding to the promoter of Brachyury leads to repression of this gene, thus disrupting mesendoderm transition.http://dx.doi.org/10.1155/2014/379678
spellingShingle Sergio Mora-Castilla
Juan R. Tejedo
Rafael Tapia-Limonchi
Irene Díaz
Ana B. Hitos
Gladys M. Cahuana
Abdelkrim Hmadcha
Franz Martín
Bernat Soria
Francisco J. Bedoya
Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation
Stem Cells International
title Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation
title_full Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation
title_fullStr Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation
title_full_unstemmed Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation
title_short Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation
title_sort transient downregulation of nanog and oct4 induced by deta no exposure in mouse embryonic stem cells leads to mesodermal endodermal lineage differentiation
url http://dx.doi.org/10.1155/2014/379678
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