Mus musculus
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PROVIDER: PRJNA153491 | ENA |
REPOSITORIES: ENA
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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.
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2005-01-01 | MODEL1305010000 | BioModels
Project description:mouse embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells were compared via metabolomic analysis
2018-08-02 | MSV000082680 | GNPS
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:Transfer of somatic cell nuclei to enucleated eggs or ectopic expression of specific transcription factors are two different reprogramming strategies used to generate pluripotent cells from differentiated cells. However, they are poorly efficient and other unknown factors might be required to increase their success rate. Here, we show that Xenopus egg extracts at the metaphase stage (M phase) have a strong reprogramming activity on mouse embryonic fibroblasts (MEFs). First, they reset replication properties of MEF nuclei toward a replication profile characteristic of early development and they erase several epigenetic marks, such as trimethylation of H3K9, H3K4 and H4K20. Second, when MEFs are reversibly permeabilized in the presence of M phase Xenopus egg extracts, they show a transient increase in cell proliferation, form colonies and start to express specific pluripotency markers. Finally, transient exposure of MEF nuclei to M phase Xenopus egg extracts increases the success of nuclear transfer to enucleated mouse oocytes and strongly synergize with the production of pluripotent stem cells by ectopic expression of transcription factors. The mitotic stage of the egg extract is crucial as neither of these effects is detected when using interphasic Xenopus egg extracts. Our data demonstrate that mitosis is essential to make mammalian somatic nuclei prone to reprogramming and that, surprisingly, the heterologous Xenopus system has features that are conserved enough to remodel mammalian nuclei. MEF cells were infected by retroviruses encoding for Oct4, Sox2, Klf4 and c-Myc and, then reversibly permeabilized and treated with Xenopus M-phase extract. All samples of each cell type (e.g. untreated MEF, ES cells and M-iPS cells) were made in triplicates. Total RNAs were extracted with RNeasy kit and hybridized on Nimblegen MM9 microarrays.
2011-11-21 | E-GEOD-31691 | biostudies-arrayexpress
Project description:In several metazoans the number of active replication origins in embryonic nuclei is higher than in somatic ones, ensuring rapid genome duplication during synchronous embryonic cell divisions. High replication origin density can be restored by somatic nuclear reprogramming. However, mechanisms underlying high replication origin density formation coupled to rapid cell cycles are poorly understood. Here, we characterized a fraction of Xenopus egg extract able to stimulate somatic DNA replication.
2020-03-19 | PXD017383 | Pride
Project description:Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource for regenerative medicine. However, genetic manipulation and difficult-to-manufacture strategies used in reprogramming limit their clinical applications. Here, we show pluripotency can be induced from mouse somatic cells by specific small-molecule compounds. The completely chemically-induced pluripotent stem cells (CiPSCs) can be stably maintained in embryonic stem cell (ESC) culture medium and resemble ESCs in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. These findings suggest that exogenous master genes are dispensable for cell fate reprogramming and pave the way for the clinical application of somatic reprogramming techniques. Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource for regenerative medicine. However, genetic manipulation and difficult-to-manufacture strategies used in reprogramming limit their clinical applications. Here, we show pluripotency can be induced from mouse somatic cells by specific small-molecule compounds. The completely chemically-induced pluripotent stem cells (CiPSCs) can be stably maintained in embryonic stem cell (ESC) culture medium and resemble ESCs in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. These findings suggest that exogenous master genes are dispensable for cell fate reprogramming and pave the way for the clinical application of somatic reprogramming techniques. Chemicals' acronyms: V, VPA; C, CHIR; 6, 616452; T, tranylcypromine; F, FSK; Z, DZNep; P, PGE2; R, RG108; S, SRT1720; M, 2-Me-5HT; D, D4476; B, Sodium butyrate. To compare the global gene expression pofile of mouse embryonic fibroblasts (MEFs), mouse adult lung fibroblasts (MAFs), mouse neonatal fibroblasts (MNFs), adipose-derived stem cells (ADSCs), chemical induced pluripotent stem cells (CiPS), embryonic stem cells (ESCs) and OSKM-iPSCs. We profiled the mRNA expression of each sample by microarray (Mouse OneArray® v2, Phalanx). Different sample set was normalized for different purpose. Set1: MEFs1, CiPS34, MNF CIPS7, CiPS50 CiPS21, OSKM-iPS1 and ESCs1 were analyzed, each sample have three replicates; Set2: MNFs, MAFs, ADSCs, MNF CiPS1, MAF CiPS3, CiPS45, ADSC CiPS2, OSKM iPS2 and ESCs2 were analyzed, each sample have three replicates; Set3: WT MEFs, ESCs3, CiPS WT1 and CiPS WT2 were analyzed, each sample have two replicates; Set4: MEFs2, SKM-FSK1, SKM-FSK2 and ESCs4 were analyzed, each sample have three replicates; Set5: MEFs3, ESCs5, CiPSCs, D12, D20 and D32 were analyzed, each sample have two replicates.
2013-07-22 | E-GEOD-48201 | biostudies-arrayexpress
Project description:Transfer of somatic cell nuclei to enucleated eggs or ectopic expression of specific transcription factors are two different reprogramming strategies used to generate pluripotent cells from differentiated cells. However, they are poorly efficient and other unknown factors might be required to increase their success rate. Here, we show that Xenopus egg extracts at the metaphase stage (M phase) have a strong reprogramming activity on mouse embryonic fibroblasts (MEFs). First, they reset replication properties of MEF nuclei toward a replication profile characteristic of early development and they erase several epigenetic marks, such as trimethylation of H3K9, H3K4 and H4K20. Second, when MEFs are reversibly permeabilized in the presence of M phase Xenopus egg extracts, they show a transient increase in cell proliferation, form colonies and start to express specific pluripotency markers. Finally, transient exposure of MEF nuclei to M phase Xenopus egg extracts increases the success of nuclear transfer to enucleated mouse oocytes and strongly synergize with the production of pluripotent stem cells by ectopic expression of transcription factors. The mitotic stage of the egg extract is crucial as neither of these effects is detected when using interphasic Xenopus egg extracts. Our data demonstrate that mitosis is essential to make mammalian somatic nuclei prone to reprogramming and that, surprisingly, the heterologous Xenopus system has features that are conserved enough to remodel mammalian nuclei.
2011-11-21 | GSE31691 | GEO
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 Myc-chromatin interactions in reprogramming cells
2015-04-15 | E-GEOD-67694 | biostudies-arrayexpress
Project description:Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource for regenerative medicine. However, genetic manipulation and difficult-to-manufacture strategies used in reprogramming limit their clinical applications. Here, we show pluripotency can be induced from mouse somatic cells by specific small-molecule compounds. The completely chemically-induced pluripotent stem cells (CiPSCs) can be stably maintained in embryonic stem cell (ESC) culture medium and resemble ESCs in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. These findings suggest that exogenous master genes are dispensable for cell fate reprogramming and pave the way for the clinical application of somatic reprogramming techniques. Chemicals' acronym: V, VPA; C, CHIR; 6, 616452; T, tranylcypromine; F, FSK; Z, DZNep; P, PGE2; R, RG108; S, SRT1720; M, 2-Me-5HT; D, D4476; B, Sodium butyrate. mRNA expression analysis of mouse embryonic fibroblasts (MEFs), GFP- cells, GFP+ clusters,GFP+ colonies, embryonic stem cells (ESCs) and CiPSCs by RNA sequencing.
2013-07-22 | E-GEOD-48252 | biostudies-arrayexpress
Project description:Genome-wide analysis of two parental human embryonic stem cell (ESC) lines (hESM01 and n5), three n5-derived somatic cell lines (N-neurons, F-fibroblasts, R-retinal pigment epithelium), and three pairs of induced pluripotent stem cell (iPSC) clones (iN, iF, iR) at gene expression level. All lines are isogenic. In the present study an accuracy of reprogramming was tested and a universal signature of iPSCs was found. Total RNA obtained from isogenic cell lines compared to each other. For each line there are a biological (different passages) or technical (same passage) replicate.
2015-07-15 | E-GEOD-70735 | biostudies-arrayexpress