title: Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation.
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.
authors.affiliation: Andalusian 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, Spain ; Sanford Consortium for Regenerative Medicine, University of California San Diego, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Mora-Castilla
authors.affiliation: Andalusian 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, Spain.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Tejedo
authors.affiliation: Andalusian 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, Spain.
authors.forename: Rafael
authors.identifier: 0000-0001-7483-1729
authors.initials: R
authors.lastname: Tapia-Limonchi
authors.affiliation: Andalusian 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, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Díaz
authors.affiliation: Andalusian 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, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Hitos
authors.affiliation: Andalusian 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, Spain.
authors.forename: Gladys M
authors.initials: GM
authors.lastname: Cahuana
authors.affiliation: Andalusian 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, Spain.
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Hmadcha
authors.affiliation: Andalusian 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, Spain.
authors.forename: Franz
authors.initials: F
authors.lastname: Martín
authors.affiliation: Andalusian 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, Spain.
authors.forename: Bernat
authors.initials: B
authors.lastname: Soria
authors.affiliation: Andalusian 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, Spain.
authors.forename: Francisco J
authors.identifier: 0000-0003-0262-7029
authors.initials: FJ
authors.lastname: Bedoya