Disease relevance of Nanog

• The expression of oct4, stella, fragilis was detected in the teratomas, but nanog was not expressed [1].

High impact information on Nanog

• We identified 1,083 and 3,006 high-confidence binding sites for Oct4 and Nanog, respectively [2].
• The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells [2].
• Instead we find that Wnt pathway activation by 6-bromoindirubin-3'-oxime (BIO), a specific pharmacological inhibitor of glycogen synthase kinase-3 (GSK-3), maintains the undifferentiated phenotype in both types of ESCs and sustains expression of the pluripotent state-specific transcription factors Oct-3/4, Rex-1 and Nanog [3].
• Extracellular signals and second messengers modulate cell-autonomous regulators such as OCT4, SOX2 and Nanog in a combinatorial complexity [4].
• p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression [5].

Biological context of Nanog

• The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination [2].
• Both the Oct4 and Nanog genes are direct targets of GCNF repression during ES cell differentiation and early mouse embryonic development [6].
• Elevated level of Nanog can maintain the mouse ES cell self-renewal independent of LIF and enable human ES cell growth without feeder cells [7].
• We confirm this prediction by overexpressing the H3-specific arginine methyltransferase CARM1 in individual blastomeres and show that this directs their progeny to the ICM and results in a dramatic upregulation of Nanog and Sox2 [8].
• Several extrinsic signals such as LIF, BMP and Wnt can support the self-renewal and pluripotency of embryonic stem (ES) cells through regulating the "pluripotent genes." A unique homeobox transcription factor, Nanog, is one of the key downstream effectors of these signals [7].

Anatomical context of Nanog

• Thus, Cdx2 is essential for segregation of the ICM and TE lineages at the blastocyst stage by ensuring repression of Oct4 and Nanog in the TE [9].
• Nanog expression in mouse germ cell development [10].
• Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation [11].
• Furthermore, reactivation of the somatic cell-derived Nanog was tightly linked with nuclear reprogramming induced by cell hybridization with ES cells and by nuclear transplantation into enucleated oocytes [12].
• Exogenous expression of Oct-3/4 or the dominant-negative mutant of STAT3 (STAT3F) by conventional Ad vectors containing the EF-1alpha promoter promoted the differentiation of mES cells into the cells of three germ layers, and STAT3F-mediated differentiation was rescued by the coexpression of Nanog [13].

Associations of Nanog with chemical compounds

• By employing multiparameter sorting, we identified in murine bone marrow (BM) a homogenous population of rare ( approximately 0.02% of BMMNC) Sca-1(+)lin(-)CD45(-) cells that express by RQ-PCR and immunohistochemistry markers of pluripotent stem cells (PSC) such as SSEA-1, Oct-4, Nanog and Rex-1 [14].
• Pharmacological blockade of mGlu5 receptors with 2-methyl-6-(phenylethynyl)pyridine (MPEP) or antisense-induced knock-down of mGlu5 receptors decreased the expression of the two main transcription factors that sustain ES cell self-renewal, i.e. Oct-4 and Nanog, as assessed by real-time PCR and immunoblotting [15].
• In contrast to other pluripotent stem cell-specific genes such as Oct-4 and Nanog, the Ant4 gene was readily derepressed in differentiated cells after 5-aza-2'-deoxycytidine treatment [16].
• The expression of ENK is markedly higher in undifferentiated ES cells than in retinoic acid differentiated ES cells and embryonic bodies [17].
• To further evaluate the value of Dmp in opioid peptides, we investigated Dmp(1)-substituted analogues of the delta receptor ligands, deltorphin II (DLT: Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH(2)) and enkephalin (ENK: Tyr-Gly-Gly-Phe-Leu) [18].

Physical interactions of Nanog

• Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells [19].
• These results suggest that Nanog interacts with Nac1 through WNAAP to regulate the cell cycle of ES cells via the ERas/phosphatidylinositol 3-kinase/Akt pathway, but not pluripotency, thus decoupling cell cycle control from pluripotency [20].

Regulatory relationships of Nanog

• Here, we show that Nanog expression is up-regulated in mouse ES cells by the binding of T (Brachyury) and STAT3 to an enhancer element in the mouse Nanog gene [19].
• We also show that Cripto can regulate the critical stem cell gene Nanog and two Oct 4-regulated genes: Dppa2 and 4 [21].

Other interactions of Nanog

• Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts, and transcription factors Oct-3/4, Nanog, Sox2, and STAT3, are essential for their self-renewal [22].
• Oct4 and Nanog are transcription factors required to maintain the pluripotency and self-renewal of embryonic stem (ES) cells [2].
• Our analysis further suggested that the Nanog regulatory pathway was relatively independent of the LIF/Oct pathway and may interact with the Nodal/transforming growth factor-beta pathway [23].
• The rapid down-regulation of Nanog mRNA during ESC differentiation correlates with the induction of p53 transcriptional activity and Ser 315 phosphorylation [5].
• Reduction in Nanog expression correlated with induction of extraembryonic endoderm genes GATA4, GATA6, and laminin B1, with subsequent generation of groups of cells with parietal endoderm phenotype [24].
• Our data demonstrate that the mSin3A-HDAC complex can positively regulate Nanog expression under proliferating conditions and that this activity is complementary to mSin3A-mediated p53-dependent silencing of Nanog during differentiation [25].

Analytical, diagnostic and therapeutic context of Nanog

• Reverse transcriptase-PCR and Northern blot analyses show that ENK is preferentially expressed in pre-implantation mouse embryos and a higher level in blastocysts [17].
• Whole-mount in situ hybridization analysis further demonstrates that ENK mRNA is present predominantly in the inner cell mass of blastocysts [17].

References