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

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Date

2014-12-03

Authors

Mora-Castilla, Sergio
Tejedo, Juan R
Tapia-Limonchi, Rafael
Díaz, Irene
Hitos, Ana B
Cahuana, Gladys M
Hmadcha, Abdelkrim
Martín, Franz
Soria, Bernat
Bedoya, Francisco J

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Hindawi Publishing Corporation
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Abstract

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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Journal Article;

MeSH Terms

Medical Subject Headings::Anatomy::Cells::Stem Cells::Pluripotent Stem Cells::Embryonic Stem Cells::Mouse Embryonic Stem Cells
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line
Medical Subject Headings::Anatomy::Embryonic Structures::Germ Layers::Endoderm
Medical Subject Headings::Anatomy::Embryonic Structures::Germ Layers::Mesoderm
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Fetal Proteins
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins::Histones
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::T-Box Domain Proteins

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Keywords

Células madre embrionarias, Línea celular, Endodermo, Proteínas Fetales, Histonas

Citation

Mora-Castilla S, Tejedo JR, Tapia-Limonchi R, Díaz I, Hitos AB, Cahuana GM, et al. Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation. Stem Cells Int; 2014:379678