Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA154619 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR345532.fastq.gz | Fastqsanger.gz | |||
| SRR345533.fastq.gz | Fastqsanger.gz | |||
| SRR345534.fastq.gz | Fastqsanger.gz | |||
| SRR345535.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE30995: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [RNA-Seq] GSE31006: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [ChIP-Seq] GSE31007: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [protein binding microarray] GSE31948: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [AS microarray] Refer to individual Series
2011-09-14 | E-GEOD-30992 | biostudies-arrayexpress
Project description:An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming
| PRJNA146165 | ENA
Project description:An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [RNA-Seq]
| PRJNA154623 | ENA
Project description:An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [AS microarray]
| PRJNA155297 | ENA
Project description:An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [protein binding microarray]
| PRJNA154621 | ENA
Project description:Chickarmane2008 - Stem cell lineage - NANOG GATA-6 switch
In this work, a dynamical model of lineage
determination based upon a minimal circuit, as discussed in PMID: 17215298
, which contains the Oct4/Sox2/Nanog core as well its interaction
with a few other key genes is discussed.
This model is described in the article:
A computational model for understanding stem cell, trophectoderm and endoderm lineage determination.
Chickarmane V, Peterson C
PloS one. 2008, 3(10):e3478
Abstract:
BACKGROUND: Recent studies have associated the transcription factors, Oct4, Sox2 and Nanog as parts of a self-regulating network which is responsible for maintaining embryonic stem cell properties: self renewal and pluripotency. In addition, mutual antagonism between two of these and other master regulators have been shown to regulate lineage determination. In particular, an excess of Cdx2 over Oct4 determines the trophectoderm lineage whereas an excess of Gata-6 over Nanog determines differentiation into the endoderm lineage. Also, under/over-expression studies of the master regulator Oct4 have revealed that some self-renewal/pluripotency as well as differentiation genes are expressed in a biphasic manner with respect to the concentration of Oct4. METHODOLOGY/
PRINCIPAL FINDINGS: We construct a dynamical model of a minimalistic network, extracted from ChIP-on-chip and microarray data as well as literature studies. The model is based upon differential equations and makes two plausible assumptions; activation of Gata-6 by Oct4 and repression of Nanog by an Oct4-Gata-6 heterodimer. With these assumptions, the results of simulations successfully describe the biphasic behavior as well as lineage commitment. The model also predicts that reprogramming the network from a differentiated state, in particular the endoderm state, into a stem cell state, is best achieved by over-expressing Nanog, rather than by suppression of differentiation genes such as Gata-6.
CONCLUSIONS: The computational model provides a mechanistic understanding of how different lineages arise from the dynamics of the underlying regulatory network. It provides a framework to explore strategies of reprogramming a cell from a differentiated state to a stem cell state through directed perturbations. Such an approach is highly relevant to regenerative medicine since it allows for a rapid search over the host of possibilities for reprogramming to a stem cell state.
This model is hosted on BioModels Database
and identified
by: MODEL8389825246
.
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 | BIOMD0000000210 | BioModels
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
.
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:Alternative RNA splicing (AS) regulates proteome diversity, including isoform-specific expression of several pluripotency genes. Here, we integrated global gene expression and proteomic analyses and identified a molecular signature suggesting a central role for AS in maintaining human pluripotent stem cell (hPSC) self-renewal. We demonstrate the splicing factor SFRS2 is an OCT4 target gene required for pluripotency. SFRS2 regulates AS of the methyl-CpG-binding protein MBD2, whose isoforms play opposing roles in maintenance of, and reprogramming to, pluripotency. While both MDB2a and MBD2c are enriched at the OCT4 and NANOG promoters, MBD2a preferentially interacts with repressive NuRD chromatin remodeling factors and promotes hPSC differentiation, whereas overexpression of MBD2c enhances reprogramming of fibroblasts to pluripotency. The miR-301 and miR-302 families provide additional regulation by targeting SFRS2 and MDB2a. These data suggest that OCT4, SFRS2, and MBD2 participate in a positive feedback loop, regulating proteome diversity complexity in support of hPSC self-renewal and reprogramming. We isolated RNA from human fibroblasts and human embryonic stem cells for hybridization to the Affymetrix gene expression microarrays.
2014-04-20 | E-GEOD-55678 | biostudies-arrayexpress
Project description:Embryonic stem cells are maintained in a self-renewing and pluripotent state by multiple regulatory pathways. Pluripotent-specific transcriptional networks are sequentially reactivated as somatic cells reprogram to achieve pluripotency. How epigenetic regulators modulate this process and contribute to somatic cell reprogramming is not clear. Here we perform a functional RNAi screen to identify the earliest epigenetic regulators required for reprogramming. We identify components of the SAGA histone acetyltransferase complex, in particular Gcn5, as critical regulators of reprogramming initiation. Furthermore, we show in mouse pluripotent stem cells that Gcn5 strongly associates with Myc and that upon initiation of somatic reprogramming, Gcn5 and Myc form a positive feed forward loop that activates a distinct alternative splicing network and the early acquisition of pluripotency-associated splicing events. These studies expose a Myc-SAGA pathway that drives expression of an essential alternative splicing regulatory network during somatic cell reprogramming. Examination of 2 Gcn5-chromatin interactions in mouse embryonic stem cells
2015-04-15 | E-GEOD-67710 | biostudies-arrayexpress
Project description:Previous investigations of the core gene regulatory circuitry that controls embryonic stem cell (ESC) pluripotency have largely focused on the roles of transcription, chromatin and non- coding RNA regulators. Alternative splicing (AS) represents a widely acting mode of gene regulation, yet its role in the regulation of ESC pluripotency and differentiation is poorly understood. Here, we identify the Muscleblind-like RNA binding proteins, MBNL1 and MBNL2, as conserved and direct negative regulators of a large program of AS events that are differentially regulated between ESCs and other cell types. Knockdown of MBNL proteins in differentiated cells causes switching to an ESC-like AS pattern for at least half of these AS events. Among the events is an ESC-specific AS switch in the forkhead family transcription factor FOXP1 that controls pluripotency. Consistent with a central and negative regulatory role for MBNL proteins in pluripotency, their knockdown significantly enhances the expression of key pluripotency genes and the formation of induced pluripotent stem cells (iPSCs) during somatic cell reprogramming. mRNA profiles of various embryonic stem cells, tissues and cell lines from human and mouse using high-throughput sequencing data and the role of MBNL proteins in regulation of ESC-differential alternative splicing
2013-06-26 | E-GEOD-45503 | biostudies-arrayexpress