NANOG amplifies STAT3 activation and they synergistically induce the naïve pluripotent program
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE53529 | GEO | 2014/01/06
SECONDARY ACCESSION(S): PRJNA232300
REPOSITORIES: GEO
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Project description:We generated Nanog-/- iPSCs from both EpiSCs and pre-iPSCs. We wanted to compare the global gene expression profile of these iPSCs to their parental cells lines and to wild-type and Nanog-/- ESCs. We analysed two technical replicates of each cell line.
2014-01-06 | E-GEOD-53529 | biostudies-arrayexpress
Project description:Reprogramming of a differentiated cell back to a naive pluripotent identity is thought to occur by several independent mechanisms. Two such mechanisms include NANOG and activated STAT3 (pSTAT3), known master regulators of naive pluripotency acquisition [1-5]. Here, we investigated the relationship between NANOG and pSTAT3 during the establishment and maintenance of naive pluripotency. Surprisingly, we found that NANOG enhances LIF signal transduction, resulting in elevated pSTAT3. This is mediated, at least in part, by suppression of the expression of the LIF/STAT3 negative regulator SOCS3. We also discovered NANOG to be limiting for the expression of KLF4, a canonical "Yamanaka" reprogramming factor [6] and key pSTAT3 target [2, 7, 8]. KLF4 expression resulted from the codependent and synergistic action of NANOG and pSTAT3 in embryonic stem cells and during initiation of reprogramming. Additionally, within 48 hr, the combined actions of NANOG and pSTAT3 in a reprogramming context resulted in reactivation of genes associated with naive pluripotency. Importantly, we show that NANOG can be bypassed during reprogramming by exogenous provision of its downstream effectors, namely pSTAT3 elevation and KLF4 expression. In conclusion, we propose that mechanisms of reprogramming are linked, rather than independent, and are centered on a small number of genes, including NANOG.
| S-EPMC3982126 | biostudies-literature
Project description:Cellular reprogramming from somatic cells to induced pluripotent stem cells (iPSCs) can be achieved through forced expression of the transcription factors Oct4, Klf4, Sox2 and c-Myc (OKSM). These factors, in combination with environmental cues, induce a stable intrinsic pluripotency network that confers indefinite self-renewal capacity on iPSCs. In addition to Oct4 and Sox2, the homeodomain-containing transcription factor Nanog is an integral part of the pluripotency network. Although Nanog expression is not required for the maintenance of pluripotent stem cells, it has been reported to be essential for the establishment of both embryonic stem cells (ESCs) from blastocysts and iPSCs from somatic cells. Here we revisit the role of Nanog in direct reprogramming. Surprisingly, we find that Nanog is dispensable for iPSC formation under optimized culture conditions. We further document that Nanog-deficient iPSCs are transcriptionally highly similar to wild-type iPSCs and support the generation of teratomas and chimeric mice. Lastly, we provide evidence that the presence of ascorbic acid in the culture media is critical for overcoming the previously observed reprogramming block of Nanog knockout cells. Comparison of Nanog KO iPSCs to WT pluripotent cells.
2014-01-28 | E-GEOD-53832 | biostudies-arrayexpress
Project description:To investigate the molecular mechanisms underlying the reprogramming of epiblast stem cells (EpiSCs) into embryonic stem cells (ESCs) induced by Esrrb, we performed ChIP-seq analysis of Esrrb, Nanog, Oct4, and Sox2 in Tet-on Esrrb EpiSCs after treatment with doxycycline (Dox).
2018-06-01 | E-MTAB-5342 | biostudies-arrayexpress
Project description:Cellular reprogramming from somatic cells to induced pluripotent stem cells (iPSCs) can be achieved through forced expression of the transcription factors Oct4, Klf4, Sox2 and c-Myc (OKSM). These factors, in combination with environmental cues, induce a stable intrinsic pluripotency network that confers indefinite self-renewal capacity on iPSCs. In addition to Oct4 and Sox2, the homeodomain-containing transcription factor Nanog is an integral part of the pluripotency network. Although Nanog expression is not required for the maintenance of pluripotent stem cells, it has been reported to be essential for the establishment of both embryonic stem cells (ESCs) from blastocysts and iPSCs from somatic cells. Here we revisit the role of Nanog in direct reprogramming. Surprisingly, we find that Nanog is dispensable for iPSC formation under optimized culture conditions. We further document that Nanog-deficient iPSCs are transcriptionally highly similar to wild-type iPSCs and support the generation of teratomas and chimeric mice. Lastly, we provide evidence that the presence of ascorbic acid in the culture media is critical for overcoming the previously observed reprogramming block of Nanog knockout cells.
2014-01-28 | GSE53832 | GEO
Project description:It has been suggested that the transcription factor Nanog is essential for the establishment of pluripotency during the derivation of embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. However, successful reprogramming to pluripotency with a growing list of divergent transcription factors, at ever increasing efficiencies, suggests that there may be many distinct routes to a pluripotent state. Here, we have investigated whether Nanog is necessary for reprogramming murine fibroblasts under highly efficient conditions using the canonical reprogramming factors Oct4, Sox2, Klf4 and cMyc. In agreement with prior results, the efficiency of reprogramming Nanog-/- fibroblasts was significantly lower than that of control fibroblasts. However, in contrast to previous findings, we were able to reproducibly generate iPS cells from Nanog-/- fibroblasts that effectively contributed to chimeric mice. Thus while Nanog may be an important mediator of reprogramming it is not required for establishing pluripotency in the mouse, even under standard conditions. In order to further evaluate the equivalency of Nanog null iPSC to nanog null ESCs, we have performed RNAseq on two independent nanog null iPSC lines, as well as Nanog Null ESC, WT ESC and iPSCs as well as MEFs. As a negativve control for reprogramming we have analyzed a partially reprogrammed iPSC line. 2-4 biological replicates each of 7 conditions (WT MEFs, WT ESC, WT iPSC, WT partially reprogrammed iPSC (piPS), Nanog null ESC, Nanog null iPSC clone G2 and Nanog null iPSC clone G5)
2014-01-01 | E-GEOD-53212 | biostudies-arrayexpress
Project description:To reveal a gene expression signature associated with developmental competence, we selected the following groups of iPSC lines for microarray analysis. i) “Poor quality” iPSCs: This group included the three OSKM-iPSC lines Nanog-GFP OSKM#2, Oct4-GFP OSKM#2 and KH2 OSKM27, that either did not produce fully developed pups or produced very low number of pups; ii) “Good quality” iPSCs: This group included BC_2 OSKM28 and Nanog-GFP SNEL#3, both of which gave rise to live, normal pups that survived only few hours; iii) “High quality” iPSCs consisting of Nanog-GFP SNEL#2 and Oct4-GFP SNEL#1, both of which generated live pups that survived postnatally (representative pups from each iPSC group are shown in Figure S5). iv) As controls we used Nanog-GFP, Oct4-GFP and KH229 ESCs.
2014-09-08 | GSE45173 | GEO
Project description:It has been suggested that the transcription factor Nanog is essential for the establishment of pluripotency during the derivation of embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. However, successful reprogramming to pluripotency with a growing list of divergent transcription factors, at ever increasing efficiencies, suggests that there may be many distinct routes to a pluripotent state. Here, we have investigated whether Nanog is necessary for reprogramming murine fibroblasts under highly efficient conditions using the canonical reprogramming factors Oct4, Sox2, Klf4 and cMyc. In agreement with prior results, the efficiency of reprogramming Nanog-/- fibroblasts was significantly lower than that of control fibroblasts. However, in contrast to previous findings, we were able to reproducibly generate iPS cells from Nanog-/- fibroblasts that effectively contributed to chimeric mice. Thus while Nanog may be an important mediator of reprogramming it is not required for establishing pluripotency in the mouse, even under standard conditions. In order to further evaluate the equivalency of Nanog null iPSC to nanog null ESCs, we have performed RNAseq on two independent nanog null iPSC lines, as well as Nanog Null ESC, WT ESC and iPSCs as well as MEFs. As a negativve control for reprogramming we have analyzed a partially reprogrammed iPSC line.
2014-01-01 | GSE53212 | GEO
Project description:Modified sea anemone vent reprogrammed nanog-null iPSCs
| PRJEB51885 | ENA
Project description:We have investigated the functional relevance of the transcriptional network controlled by the Otx2 binding activity in ESCs, EpiSCs and in vivo. In particular, to study the Otx2 transcriptional network we first performed Otx2 chromatin immunoprecipitation sequencing (ChIP-seq) experiments in wt ESCs and day 4 (d4) ESC-derived EpiSCs and employed as negative control ESCs and EpiSCs lacking Otx2. Moreover, to investigate the functional relevance of the Otx2 binding activity in pluripotent stem cells, we mutagenized in ESCs the Otx2 binding site located upstream of the Nanog TSS. To characterize the identity of ESCs and EpiSCs both lacking this Otx2 binding site, we analyzed their transcriptome by RNA-Seq.
2016-06-09 | E-MTAB-3856 | biostudies-arrayexpress