Objective: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to combine computational fluid dynamic (CFD) simulations with global microarray analysis to study flow-dependent vessel wall biology in portions of the entire aorta under physiological conditions. Methods and Results: Animal-specific WSS magnitude and vector direction were estimated using CFD based on aortic geometry and flow information acquired by MRI. Two distinct flow pattern regions were identified in the normal rat aorta; the distal part of the inner curvature being exposed to low WSS and a non-uniform vector direction, and a region along the outer curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis identified numerous novel mechanosensitive genes, including Hand2, trpc4 and slain2, and confirmed well-known ones, such as klf2 and BMP4. Three genes were further validated for protein , including Hand2, which showed higher expression in the endothelium in regions exposed to disturbed flow. Gene ontology analysis revealed an over-representation of genes involved in transcriptional regulation.
Characterization of shear-sensitive genes in the normal rat aorta identifies Hand2 as a major flow-responsive transcription factor.
Specimen part
View SamplesAoSMC and FB were cultured and exposed to transforming growth factor beta1 (TGFb1) prior to the exon array analysis
Aneurysm development in patients with a bicuspid aortic valve is not associated with transforming growth factor-β activation.
Sex, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break.
No sample metadata fields
View SamplesGenome integrity is fundamental for cell survival and cell cycle progression. Important mechanisms for keeping the genome intact are proper sister chromatid segregation, correct gene regulation and efficient repair of damaged DNA. Cohesin and its DNA loader, the Scc2/4 complex have been implicated in all these cellular actions. The gene regulation role has been described in several organisms. In yeast it has been suggested that the proteins in the cohesin network would effect transcription based on its role as insulator. More recently, data are emerging indicating direct roles for gene regulation also in yeast. Here we extend these studies by investigating whether the cohesin loader Scc2 is involved in regulation of gene expression. We performed global gene expression profiling in the absence and presence of DNA damage, in wild type and Scc2 deficient G2/M arrested cells, when it is known that Scc2 is important for DNA double strand break repair and formation of damage induced cohesion. We found that not only the DNA damage specific transcriptional response is distorted after inactivation of Scc2, but also the overall transcription profile. Interestingly, these alterations did not correlate with changes in cohesin binding.
Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break.
No sample metadata fields
View SamplesThe yeast Mediator complex can be divided into three modules, designated Head, Middle and Tail. Tail comprises the Med2, Med3, Med5, Med15 and Med16 protein subunits, which are all encoded by genes that are individually non-essential for viability. In cells lacking Med16, Tail is displaced from Head and Middle. However, inactivation of MED5/MED15 and MED15/MED16 are synthetically lethal, indicating that Tail performs essential functions as a separate complex even when it is not bound to Middle and Head. We have used the N-Degron method to create temperature sensitive (ts) mutants in the Mediator tail subunits Med5, Med15 and Med16 to study the immediate effects on global gene expression when each subunit is individually inactivated, and when MED5/15 or MED15/16 are inactivated together.
Functional studies of the yeast med5, med15 and med16 mediator tail subunits.
No sample metadata fields
View SamplesAdipose tissue from 6 non-obese patients was collagenase treated and adipocytes separated from the stromal vascular fraction(SVF). SVF was then FACS sorted for the following fractions CD45-/CD34+/CD31+ (endothelial), CD45-/CD34+/CD31- (progenitor), CD45+/CD14+ (monocyte/macrophage), CD45+/CD14-(Leukocyte). RNA was isolated from adipocyte, SVF, progenitor, macrophage/monocyte and leukocyte fractions and analyzed on the Affymetrix Human Transcriptome 2.0 array. We also sorted SVF from an additional 13 (10 non-obese, 9 obese) patients and sent progenitor RNA for Affymetrix Human Transcriptome 2.0 array analysis.
The cell-type specific transcriptome in human adipose tissue and influence of obesity on adipocyte progenitors.
Sex, Specimen part, Subject
View SamplesSingle cell RNA-sequencing of human tonsil Innate lymphoid cells (ILCs) from three independent tonsil donors. Overall design: Sequencing libraries were prepared from FACS sorted individual ILCs with the Smart-Seq2 protocol (Picelli et al. Nature Methods 2013)
The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing.
No sample metadata fields
View SamplesWe investigated gene expression signatures in subcutaneous adipose tissue obtained from control subjects, premanifest HD gene carriers and manifest HD subjects with the aim to identify gene expression changes and signalling pathway alterations in adipose tissue relevant to HD.
Analysis of White Adipose Tissue Gene Expression Reveals CREB1 Pathway Altered in Huntington's Disease.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epithelial and stromal microRNA signatures of columnar cell hyperplasia linking Let-7c to precancerous and cancerous breast cancer cell proliferation.
Sex, Specimen part, Disease, Disease stage, Treatment
View SamplesWe ovexpressed human alpha synuclein alone or together with Nurr1 in mouse primary midbrain cultures and identified the full spectrum of genes whose expression is affected by alpha synuclein, including genes whose expression is normalized after Nurr1 overexpression. Moreover we treated mouse primary midbrain cultures with Bexarotene or short hairpin RNA fro Nurr1, sorted out the dopamine neurons and assessed the effects of Bexarotene and of the Nurr1 downregulation on gene expression. Overall design: Comparison of 3 Synuclein samples to 5 controls (RFP), Comparison of 3 Synuclein + Nurr1 samples to 5 controls (RFP), Comparison of 3 Bexarotene samples to 3 controls (DMSO), comparison of 1 short hairpin against Nurr1 to 1 control (scrambled).
Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate α-Synuclein Disrupted Gene Expression.
No sample metadata fields
View Samples