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GSE19042
Mus musculus
24 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
While the hypothalamo-pituitary-adrenal axis (HPA) activates a general stress response by increasing glucocorticoid (Gc) synthesis, biological stress resulting from infections triggers the inflammatory response through production of cytokines. The pituitary gland integrates some of these signals by responding to the pro-inflammatory cytokines IL6 and LIF and to a negative Gc feedback loop. The present work used whole-genome approaches to define the LIF/STAT3 regulatory network and to delineate cross-talk between this pathway and Gc action. Genome-wide ChIP-chip identified 3 449 STAT3 binding sites, whereas 2 396 genes regulated by LIF and/or Gc were found by expression profiling. Surprisingly, LIF on its own changed expression of only 85 genes but the joint action of LIF and Gc potentiated the expression of more than a thousand genes. Accordingly, activation of both LIF and Gc pathways also potentiated STAT3 and GR recruitment to many STAT3 targets. Our analyses revealed an unexpected gene cluster that requires both stimuli for delayed activation: 83% of the genes in this cluster are involved in different cell defense mechanisms. Thus, stressors that trigger both general stress and inflammatory responses lead to activation of a stereotypic innate cellular defense response.
Publication Title
Regulatory network analyses reveal genome-wide potentiation of LIF signaling by glucocorticoids and define an innate cell defense response.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pitx3 is a transcription factor that is expressed in all midbrain dopaminergic (mDA) neurons during early development, but later becomes restricted in dopaminergic subsets of substantia nigra compacta (SNc) and of the ventral tegmental are (VTA) that are vulnerable to neurodegenerative stress (MPTP, 6-OHDA, rotenone, Parkinson's disease). Overall, in mice, Pitx3 is required for developmental survival of ventral SNc neurons and for postnatal survival of VTA neurons (after postnatal day 40). With the aim of determining the gene networks that distinguish Pitx3-vulnerable (Pitx3-positive) from Pitx3-resistant (Pitx3-negative) subsets of SNc and VTA, we performed a comparison at the transcriptome level between FAC-sorted mDA neurons of SNc and VTA that were obtained from wild-type and Pitx3-/- newborn mice. The latter mice have already lost the majority of their TH+Calb1- mDA neurons of ventral SNc (Pitx3-dependent), but their TH+Calb1+ neurons of dorsal SNc (Pitx3-independent), including all of VTA neurons (50% are Pitx3-dependent and 50% Pitx3-independent), are unaffected by Pitx3 deletion. At postnatal day 40, Pitx3-/- mice display a marked loss of dopaminergic subsets of VTA that normally co-express Pitx3 and Calb1 (Pitx3-dependent neurons of VTA).
Publication Title
Rgs6 is required for adult maintenance of dopaminergic neurons in the ventral substantia nigra.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
[original title] Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma.
Publication Title
Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 31 Downloadable Samples
Illumina HiSeq 2000
Description
Pitx1, critical regulator of a limited hindlimb-specific gene network, targets the limb development program common to both fore- and hindlimbs in order to implement hindlimb-specific limb morphology. Overall design: The gene regulatory networks governing forelimb vs. hindlimb development in mouse were investigated using expressing profiling of morphologically stage-matched e10.5 forelimbs and e11.0 hindlimbs, ChIPseq of chromatin marks, and ChIPseq of limb-specific transcription factors Pitx1 and Tbx5. The makeup of the Pitx1-directed components of the hindlimb gene network were investigated using expression profiling of Pitx1 null hindlimbs at two stages (e11.0 and e11.5).
Publication Title
Regulatory integration of Hox factor activity with T-box factors in limb development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
Deployment of a cell-specifying enhancer repertoire by the pioneer factor Pax7 The establishment and maintenance of cell identity depends on implementation of stable cell-specific chromatin landscapes. Pioneer transcription factors establish new cell fate competences by triggering chromatin remodeling during development. Here, we used pituitary cell specification to define the salient features of pioneer action. Comparison of purified pituitary cells of different lineages showed that chromatin accessibility differs at enhancers rather than promoters. The pioneer factor Pax7 specifies one pituitary lineage identity by opening a specific repertoire of enhancers that are distinct from the myogenic targets of Pax7. Pax7 binds its pioneer targets rapidly and days before chromatin remodeling and gene activation. Finally, enhancers opened by Pax7-dependent chromatin remodeling exhibit loss of DNA methylation and they acquire long term epigenetic memory. The present work identifies enhancer pioneering as a critical feature for cell fate specification and maintenance. Overall design: RNA extraction followed by high throughput sequencing (RNA-seq)
Publication Title
Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of cell fate.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
The combinatorial expression of the Hox genes along the body axes, referred to as the HOX code, is a major determinant of cell fate and plays a prevailing role in generating the animal body plan. In developing limb buds, the paralogous group 13 genes of the HoxA and HoxD clusters are essential for patterning the distal-most limb structures, the digits. Inactivation of HOXA13 and HOXD13 transcription factors (HOX13) leads to complete digit agenesis in mice, but how HOX13 regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here we performed genome-wide profiling of HOX13 by chromatin immunoprecipitation and analyzed the transcriptome and chromatin state of wild type early and late-distal limb buds, as well as Hoxa13-/-;Hoxd13-/- compound mutant limb buds. Our results show that inactivation of HOX13 impairs the activation and repression of putative cis-regulatory modules specific to the late-distal limb cells. Loss of HOX13 also disrupts the specific, spatial patterning of gene expression along the proximal-distal axis of the developing limb buds. These results show that proper termination of the early limb transcriptional program and activation of the late-distal limb program are coordinated by the dual action of HOX13 on cis-regulatory modules. Overall design: Totla mRNAs from dissected distal parts of e11.5 forelimb, of wild-type as well as Hoxa13-/-;Hoxd13-/- mice
Publication Title
Regulatory integration of Hox factor activity with T-box factors in limb development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 602 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Innovative approaches combining regulatory networks and genomic data are needed to extract pertinent biological informations to a better understanding of complex disease such as cancer and improve identi cation of entities leading to potential new therapeutic avenues. In this study, we confronted an automatic generated regulatory network with gene expression pro les (GEP) from a large cohort of patients with multiple myeloma (MM) and normal individuals with a causality reasonning method based of graph coloring to identify keynodes. Due to this causality reasoning, it is possible to infer proteins state from these GEP. Also, our method is able to simulate the impact of the perturbation of a node in this regulatory network to identify therapeutic targets. This method allowed us to nd that JUN/FOS and FOXM1, known in MM, and their inhibition as speci c to large group of patients with MM. Moreover, we associated the inhibition of FOXM1 activity with good prognosis, suggesting the inhibition of FOXM1 activity could be a survival marker. Finally, if JUN/FOS activation seems to be a way to strongly perturb the regulatory network in view of GEP, our result suggests the activation of FOXM1 could be interesting way to perturb some sub-group of profiles.
Publication Title
Logic programming reveals alteration of key transcription factors in multiple myeloma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Here we investigated the effect of stable knock-down of the NAA-catabolizing enzyme, Aspartoacylase (Aspa), on global gene expression in a brown adipocyte cell line.
Publication Title
N-acetylaspartate catabolism determines cytosolic acetyl-CoA levels and histone acetylation in brown adipocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Mouse liver tumors (T) and non tumoral adjacent livers (NT) sorted from mice knock out for Axin1 gene specifically in the hepatocytes . 3 mice of the brother hood non deleted for Axin1 were used as controls (WT)
Publication Title
AXIN deficiency in human and mouse hepatocytes induces hepatocellular carcinoma in the absence of β-catenin activation.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 51 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Analysis of the transcriptional profiles of mRNA and microRNA in Rasless fibroblasts. 4-Hydroxy-tamoxifen (4-OHT) treatment triggers removal of K-Ras expression in [H-Ras-/-;N-Ras-/-;K-Raslox/lox;RERTert/ert ] mouse fibroblasts (named K-Raslox) generating Rasless MEFs which are unable to proliferate, but recover proliferative ability after ectopic expression of constitutively active downstream kinases such as BRAF and MEK1.
Publication Title
Reversible, interrelated mRNA and miRNA expression patterns in the transcriptome of Rasless fibroblasts: functional and mechanistic implications.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples