OCT4 Knockdown in human embryonic stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE21135 | GEO | 2010/04/05
SECONDARY ACCESSION(S): PRJNA129669
REPOSITORIES: GEO
Similar Datasets
Project description:We studied the genomic locations of three key regulatory proteins (OCT4, NANOG and CTCF) in human and mouse embryonic stem (ES) cells [see Series GSE20650]. To identify the conserved and unique human OCT4 targets, we performed an OCT4 RNAi knock-down experiment. We find that species-specific transposable elements have profoundly altered the transcriptional circuitry of pluripotent stem cells. To identify the mRNA targets of OCT4: 12 samples were collected in total. Each sample is done in triplicate and samples were collected at 2 different time point, 2 days and 3 days after transfection. Luciferase knockdown serves as negative control and OCT4 knockdown is the experimental sample.
2010-04-13 | E-GEOD-21135 | biostudies-arrayexpress
Project description:The transcription factors Oct4, Sox2, and Nanog have essential roles in early development and are required for the propagation of undifferentiated embryonic stem (ES) cells in culture. To gain insights into transcriptional regulation of human ES cells, we have identified Oct4, Sox2, and Nanog target genes using genome-scale location analysis. We found, surprisingly, that Oct4, Sox2, and Nanog co-occupy a substantial portion of their target genes. These target genes frequently encode transcription factors, many of which are developmentally important homeodomain proteins. Our data also indicates that Oct4, Sox2, and Nanog collaborate to form regulatory circuitry in ES cells consisting of autoregulatory and feedforward loops. These results provide new insights into the transcriptional regulation of stem cells and reveal how Oct4, Sox2, and Nanog contribute to pluripotency and self-renewal.
2005-09-23 | E-WMIT-5 | biostudies-arrayexpress
Project description:Embryonic stem cells have a unique regulatory circuitry, largely controlled by the transcription factors Oct4, Sox2 and Nanog, which generates a gene expression program necessary for pluripotency and self-renewal (Boyer et al. 2005; Loh et al. 2006; Chambers et al. 2003; Mitsui et al. 2003; Nichols et al. 1998). How external signals connect to this regulatory circuitry to influence embryonic stem cell fate is not known. We report here that a terminal component of the canonical Wnt pathway in embryonic stem cells, the transcription factor Tcf3, co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. Thus Tcf3 is an integral component of the core regulatory circuitry of ES cells, which includes an autoregulatory loop involving the pluripotency regulators. Both Tcf3 depletion and Wnt pathway activation cause increased expression of Oct4, Nanog and other pluripotency factors and enhance pluripotency and self-renewal. Our results reveal that the Wnt pathway, through Tcf3, brings developmental signals directly to the core regulatory circuitry of ES cells to influence the balance between pluripotency and differentiation.
2008-02-28 | E-TABM-409 | biostudies-arrayexpress
Project description:Oct4, Sox2 and Nanog cooperate to form the transcriptional regulatory circuitry of embyronic stem cells. To gain insight into the genes regulated by the core circuitry of transcription factors, chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) was performed to determine the genome-wide binding targets of Oct4.
2010-05-20 | GSE21916 | GEO
Project description:Oct4, Sox2 and Nanog cooperate to form the transcriptional regulatory circuitry of embyronic stem cells. To gain insight into the genes regulated by the core circuitry of transcription factors, chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) was performed to determine the genome-wide binding targets of Oct4. DNA was enriched by chromatin immunoprecipitation (ChIP) and analyzed by Solexa sequencing. ChIP was performed using an antibody against IgG as a background control. ChIP was performed using an antibody against Oct4 in two biological replicates. The first replicate was sequenced twice (technical replicate 1 and technical replicate 2).
2010-05-20 | E-GEOD-21916 | biostudies-arrayexpress
Project description:Genome-wide approaches have begun to elucidate the transcriptional and epigenetic regulatory networks responsible for pluripotency in embryonic stem (ES) cells. Chromatin Immunoprecipitation (ChIP) followed either by hybridization to a microarray platform (ChIP-chip), or by DNA sequencing (ChIP-PET), has identified the genomic-binding targets of the ES cell transcription factors Oct4 and Nanog in humans and mice, respectively. A central issue that remains to be resolved is the concordance of the data obtained by these methods, given the differences between the two techniques. Here, we report the identification of the Oct4 and Nanog genomic targets in mouse ES cells by ChIP-Chip and have compared the data with binding data identified previously by ChIP-PET. Binding data have also been combined with Oct4 and Nanog RNAi knockdown expression profiling data in ES cells. Surprisingly, we find a substantial difference between the regions that identified exclusively by one of the two techniques. In both studies, however, targets identified by either technique contain a number of genes that are differentially expressed on Oct4 or Nanog knockdown, and have been implicated in cell-fate determination events. This study provides a comparison between the data obtained by different genomic platform, and offers a more comprehensive picture of the stem cell transcriptional network.
2008-11-04 | E-TABM-410 | biostudies-arrayexpress
Project description:Chavez2009 - a core regulatory network of OCT4 in human embryonic stem cells
A core OCT4-regulated network has been identified as a test case, to analyase stem cell characteristics and cellular differentiation.
This model is described in the article:
In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach.
Chavez L, Bais AS, Vingron M, Lehrach H, Adjaye J, Herwig R
BMC Genomics, 2009, 10:314
Abstract:
BACKGROUND: The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory network governed by the transcription factors OCT4, SOX2 and NANOG. Recent studies on reprogramming somatic cells to induced pluripotent stem cells highlight OCT4 as a key regulator of pluripotency.
RESULTS: We have carried out an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments along with promoter sequence analysis of putative target genes) and identified a core OCT4 regulatory network in human embryonic stem cells consisting of 33 target genes. Enrichment analysis with these target genes revealed that this integrative analysis increases the functional information content by factors of 1.3 - 4.7 compared to the individual studies. In order to identify potential regulatory co-factors of OCT4, we performed a de novo motif analysis. In addition to known validated OCT4 motifs we obtained binding sites similar to motifs recognized by further regulators of pluripotency and development; e.g. the heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC transcriptional activity that leads to cell growth and proliferation.
CONCLUSION: Our analysis shows how heterogeneous functional information can be integrated in order to reconstruct gene regulatory networks. As a test case we identified a core OCT4-regulated network that is important for the analysis of stem cell characteristics and cellular differentiation. Functional information is largely enriched using different experimental results. The de novo motif discovery identified well-known regulators closely connected to the OCT4 network as well as potential new regulators of pluripotency and differentiation. These results provide the basis for further targeted functional studies.
This model is hosted on BioModels Database
and identified
by: MODEL1305010000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
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To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2005-01-01 | MODEL1305010000 | BioModels
Project description:This SuperSeries is composed of the following subset Series: GSE34904: NANOG-OCT4-SOX2 Regulatory Module in Human Embryonic Stem Cells (dataset 1) GSE34912: NANOG-OCT4-SOX2 Regulatory Module in Human Embryonic Stem Cells (dataset 2) GSE34918: NANOG-OCT4-SOX2 Regulatory Module in Human Embryonic Stem Cells (dataset 3) GSE34920: NANOG-OCT4-SOX2 Regulatory Module in Human Embryonic Stem Cells (dataset 4) Refer to individual Series
2012-04-05 | E-GEOD-34921 | biostudies-arrayexpress
Project description:Chickarmane2006 - Stem cell switch reversible
Kinetic modeling approach of the transcriptional dynamics of the embryonic stem cell switch.
This model is described in the article:
Transcriptional dynamics of the embryonic stem cell switch.
Chickarmane V, Troein C, Nuber UA, Sauro HM, Peterson C
PLoS Computational Biology. 2006; 2(9):e123
Abstract:
Recent ChIP experiments of human and mouse embryonic stem cells have elucidated the architecture of the transcriptional regulatory circuitry responsible for cell determination, which involves the transcription factors OCT4, SOX2, and NANOG. In addition to regulating each other through feedback loops, these genes also regulate downstream target genes involved in the maintenance and differentiation of embryonic stem cells. A search for the OCT4-SOX2-NANOG network motif in other species reveals that it is unique to mammals. With a kinetic modeling approach, we ascribe function to the observed OCT4-SOX2-NANOG network by making plausible assumptions about the interactions between the transcription factors at the gene promoter binding sites and RNA polymerase (RNAP), at each of the three genes as well as at the target genes. We identify a bistable switch in the network, which arises due to several positive feedback loops, and is switched on/off by input environmental signals. The switch stabilizes the expression levels of the three genes, and through their regulatory roles on the downstream target genes, leads to a binary decision: when OCT4, SOX2, and NANOG are expressed and the switch is on, the self-renewal genes are on and the differentiation genes are off. The opposite holds when the switch is off. The model is extremely robust to parameter changes. In addition to providing a self-consistent picture of the transcriptional circuit, the model generates several predictions. Increasing the binding strength of NANOG to OCT4 and SOX2, or increasing its basal transcriptional rate, leads to an irreversible bistable switch: the switch remains on even when the activating signal is removed. Hence, the stem cell can be manipulated to be self-renewing without the requirement of input signals. We also suggest tests that could discriminate between a variety of feedforward regulation architectures of the target genes by OCT4, SOX2, and NANOG.
This model is hosted on BioModels Database
and identified by: MODEL7957907314
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
2024-09-02 | BIOMD0000000203 | BioModels
Project description:Chickarmane2006 - Stem cell switch irreversible
Kinetic modeling approach of the transcriptional dynamics of the embryonic stem cell switch.
This model is described in the article:
Transcriptional dynamics of the embryonic stem cell switch.
Chickarmane V, Troein C, Nuber UA, Sauro HM, Peterson C
PLoS Computational Biology. 2006; 2(9):e123
Abstract:
Recent ChIP experiments of human and mouse embryonic stem cells have elucidated the architecture of the transcriptional regulatory circuitry responsible for cell determination, which involves the transcription factors OCT4, SOX2, and NANOG. In addition to regulating each other through feedback loops, these genes also regulate downstream target genes involved in the maintenance and differentiation of embryonic stem cells. A search for the OCT4-SOX2-NANOG network motif in other species reveals that it is unique to mammals. With a kinetic modeling approach, we ascribe function to the observed OCT4-SOX2-NANOG network by making plausible assumptions about the interactions between the transcription factors at the gene promoter binding sites and RNA polymerase (RNAP), at each of the three genes as well as at the target genes. We identify a bistable switch in the network, which arises due to several positive feedback loops, and is switched on/off by input environmental signals. The switch stabilizes the expression levels of the three genes, and through their regulatory roles on the downstream target genes, leads to a binary decision: when OCT4, SOX2, and NANOG are expressed and the switch is on, the self-renewal genes are on and the differentiation genes are off. The opposite holds when the switch is off. The model is extremely robust to parameter changes. In addition to providing a self-consistent picture of the transcriptional circuit, the model generates several predictions. Increasing the binding strength of NANOG to OCT4 and SOX2, or increasing its basal transcriptional rate, leads to an irreversible bistable switch: the switch remains on even when the activating signal is removed. Hence, the stem cell can be manipulated to be self-renewing without the requirement of input signals. We also suggest tests that could discriminate between a variety of feedforward regulation architectures of the target genes by OCT4, SOX2, and NANOG.
This model is hosted on BioModels Database
and identified by: MODEL7957942740
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
2024-09-02 | BIOMD0000000204 | BioModels