Cholesterol is one of the key molecules in mammals and the most striking examples of its deficiency are the inborn errors of cholesterol biosynthesis that manifest in severe whole body phenotypes. Liver, the principal site of cholesterol homeostasis, has rarely been investigated in these defects. We thus focused on the hepatocyte-specific deletion of lanosterol 14-demethylase (CYP51) catalyzing the rate-limiting step in the post-squalene part of cholesterol synthesis.
Lessons from hepatocyte-specific Cyp51 knockout mice: impaired cholesterol synthesis leads to oval cell-driven liver injury.
Sex, Specimen part, Treatment
View SamplesUnperturbed cholesterol homeostasis is important for normal development and sexual maturation in mice. Cyp51 is the rate limiting step in the post-lanosteorl part of cholesterol biosynthesis. Unlike the full body knockout, hepatocyte specific Cyp51 knockout mice survive throughout adulthood, however their livers are severly affected. Several of the hepatocyte specific Cyp51 knockout mice develop severe liver injury or die prior to reaching adulthood (from 4-10 weeks of age; designated as runts). We aim to uncover the timing and the mechanistic background governing the liver damage and sex differences.
Disrupting Hepatocyte Cyp51 from Cholesterol Synthesis Leads to Progressive Liver Injury in the Developing Mouse and Decreases RORC Signalling.
Sex, Specimen part
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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 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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Specimen part, Cell line
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