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SRP162673
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2500
Description
The transcriptional regulator YAP orchestrates important cell functions, determining tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positively modulates the YAP mechanoresponse to substrate stiffness through actin cytoskeleton-dependent and Hippo kinase-independent mechanisms. RHO activity is necessary but not sufficient for CAV1-dependent mechanoregulation of YAP activity. Systematic quantitative interactomic studies and image-based siRNA screenings provide evidence that this actin-dependent regulation is determined by YAP interaction with the 14-3-3 protein YWHAH. Constitutive YAP activation rescued phenotypes associated with CAV1 loss, including defective ECM remodeling. CAV1-mediated control of YAP activity was validated in vivo in a model of pancreatitis-driven acinar-to-ductal metaplasia. We propose that this CAV1-YAP mechanotransduction system controls a significant share of cell programs linked to these two pivotal regulators, with potentially broad physiological and pathological implications. Overall design: RNA-Seq in WT and Cav1KO mouse embryonic fibroblasts (MEFs) cultured on stiff or soft polyacrylamide hydrogels
Publication Title
Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
We did transcription profiling on the effect of rlm1 (MAPK Slt2 transcription factor) deletion and swi3 (component of SWI/SNF complex involved in chromatin remodeling) deletion in genes involved in cell wall stress (Congo Red) response.
Publication Title
Chromatin remodeling by the SWI/SNF complex is essential for transcription mediated by the yeast cell wall integrity MAPK pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The adipose tissue is an endocrine regulator and a risk factor for atherosclerosis and cardiovascular disease when by excessive accumulation induces obesity. Although the adipose tissue is also a reservoir for stem cells (ASC) their function and stemcellness has been questioned. Our aim was to investigate the mechanisms by which obesity affects subcutaneous white adipose tissue (WAT) stem cells.
Publication Title
Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Brain tumor neurospheres (BTCSs) are cancer cells with neural stem cell-like properties found in the fatal brain tumor glioblastoma multiforme (GBM). These cells account for less than 1% of total tumor cells, are poorly differentiated and are believed to be involved in tumor induction, progression, treatment resistance and relapse. Specific miRNAs play important roles in modulating the proliferation and differentiation of neural stem cells, therefore, we aimed to identify miRNAs controlling differentiation in GBM-BTSCs through high throughput screening miRNA array profiling. We compared the miRNA expression profiles at the neurosphere state and upon 4 and 14days of differentiation by using LIMMA, finding 21 differentially expressed miRNAs : hsa-miR-103, hsa-miR-106a, hsa-miR-106b, hsa-miR-15b, hsa-miR-17, hsa-miR-19a, hsa-miR-20a, hsa-miR-25, hsa-miR-301a and hsa-miR-93 were found up-regulated upon differentiation, while hsa-miR-100, hsa-miR-1259, hsa-miR-21, hsa-miR-22, hsa-miR-221, hsa-miR-222, hsa-miR-23b, hsa-miR-27a, hsa-miR-27b, hsa-miR-29a and hsa-miR-29b were down-regulated. Expression of 11 of the 21 miRNAs was examined by qPCR and 7 of them were validated: hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222 increased their expression upon differentiation, while hsa-miR-93 and hsa-miR-106a were inhibited. Functional studies demonstrated that miR-21 over-expression induced the expression of glial and/or neuronal cell markers in the neurospheres, possibly due to SPRY1 targeting by miR-21 in these cells, while miR-221 and miR-222 inhibition at the differentiated state reduced the expression of those differentiation markers. On the other hand, miR-29a and miR-29b targeted MCL1 in the GBM neurospheres and increased apoptotic cell death.
Publication Title
Involvement of miRNAs in the differentiation of human glioblastoma multiforme stem-like cells.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
TREX2 is a keratinocyte specific 3’-deoxyribonuclease that participates in the maintenance of skin homeostasis upon damage. This transcriptome analysis identified multiple genes and pathways deregulated by TREX2 loss in the IMQ-induced psoriasis-like model in mouse skin. Overall design: mRNA sequencing of 5 biological replicates of skin from wild-type mice treated with Imiquimod and 6 of Trex2 knockout mice treated with Imiquimod
Publication Title
The Exonuclease Trex2 Shapes Psoriatic Phenotype.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), UHN Human CpG 12K Array (HCGI12K)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The iron chelator deferasirox is widely used in patients with iron overload. Patients with low-grade myelodysplastic syndromes (MDS) get transfusion dependency and need to be treated with deferasirox to avoid iron overload. Moreover, in some patients an increase in both erythroid and platelets have been observed after deferasirox therapy. However, the mechanisms involved in these clinical findings are poorly understood. The aim of this work was to analyze, in patients treated with deferasirox, the changes in the gene expression profile after receiving the treatment. A total of fifteen patients with the diagnosis of low-grade MDS were studied. Microarrays were carried out in RNA from peripheral blood before and after 14 weeks of deferasirox therapy. Changes in 1,457 genes and 54 miRNAs were observed: deferasirox induced the downregulation of genes related to the Nf kB pathway leading of an overall inactivation of this pathway. In addition, the iron chelator also downregulated gamma interferon. Altogether these changes could be related to the improvement of erythroid response observed in these patients after therapy. Moreover, the inhibition of NFE2L2/ NRF2, which was predicted in silico, could be playing a critical role in the reduction of reactive oxygen species (ROS). Of note, miR-125b, overexpressed after deferasirox treatment, could be involved in the reduced inflammation and increased hematopoiesis observed in the patients after treatment. In summary this study shows, for the first time, the mechanisms that could be governing deferasirox impact in vivo.
Publication Title
Genome-wide transcriptomics leads to the identification of deregulated genes after deferasirox therapy in low-risk MDS patients.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genome-wide expression and methylation profiling identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes (MDSs).
Publication Title
Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
G protein-coupled receptor kinase 2 (GRK2) has emerged as a key regulator of cardiac function and myocardial structure. Cardiac GRK2 is increased in heart failure and ischemia in humans, whereas genetic inhibition of GRK2 is cardioprotective in animal models of these pathologies. However, the mechanistic basis underlying these effects are not fully understood. We have used adult GRK2 hemizygous mice (GRK2+/-) as a model to assess the effects of a sustained systemic inhibition of GRK2 in heart tissue with age.
Publication Title
Downregulation of G protein-coupled receptor kinase 2 levels enhances cardiac insulin sensitivity and switches on cardioprotective gene expression patterns.
Sample Metadata Fields
Specimen part
View Samples