Background: Studies in mice have shown that PPAR is an important regulator of lipid metabolism in liver and a key transcription factor involved in the adaptive response to fasting. However, much less is known about the role of PPAR in human liver. Here we set out to study the function of PPAR in human liver via analysis of whole genome gene regulation in human liver slices treated with the PPAR agonist Wy14643.
The impact of PPARα activation on whole genome gene expression in human precision cut liver slices.
Sex, Specimen part, Treatment, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin.
Age, Specimen part, Cell line, Treatment, Time
View SamplesOne major class of anti-cancer drugs targets topoisomerase II to induce DNA double-strand breaks and cell death of fast growing cells. In vitro experiments showed that doxorubicin can induce histone eviction as well as DNA damage, while etoposide can only induce DNA damage. Here, we compare the transcription responses of different tissues to doxorubicin or etoposide treatment in vivo.
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin.
Age, Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.
Sex, Specimen part, Treatment, Subject, Time
View SamplesBackground: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA; also known as INT-747 or 6-ethyl-chenodeoxycholic acid), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA (INT-747) alters hepatic expression of many genes. However, no data are available on the effects of OCA in human liver. Here, we generated gene expression profiles in human precision-cut liver slices (hPCLS) after treatment with OCA.
Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.
Sex, Specimen part, Treatment, Time
View SamplesBackground: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA; also known as INT-747 or 6-ethyl-chenodeoxycholic acid), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA (INT-747) alters hepatic expression of many genes. However, no data are available on the effects of OCA in human liver. Here, we generated gene expression profiles in human precision-cut liver slices (hPCLS) after treatment with OCA.
Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.
Sex, Specimen part, Treatment, Subject, Time
View SamplesThe goal of this study was to compare expression profiles of B cells in the presence and absence of transcription factor MAX under normal and premalignant settings Overall design: Each genotype is represented in triplicate (cells isolated from 3 individual mice for each)
<i>Max</i> deletion destabilizes MYC protein and abrogates Eµ-<i>Myc</i> lymphomagenesis.
Specimen part, Subject
View SamplesPreviously, long-term effects on body weight and reproductive performance have been demonstrated in the chicken model of prenatal protein undernutrition by albumen removal. Introduction of such persistent alterations in phenotype suggests stable changes in gene expression. A genome-wide screening for differences in hepatic transcriptome by RNA-Seq was performed in adult Isa Brown hens (55 weeks of age). Albumen-deprived hens were created by removal of 3 ml of the albumen from fertilized eggs and replacement with saline early during embryonic development (embryonic day 1). Results were compared to mock-treated sham hens and non-treated control hens. Correlation between relative expression levels obtained from the RNA-Seq and qPCR results was very high (Pearson’s correlation coefficiënt = 0.85), confirming the validity of the RNA-Seq results. In addition, after expansion of the sample size, 7 out of 15 selected genes demonstrated the same significant gene expression differences in the qPCR as in the RNA-Seq dataset, and were thus biologically confirmed. Grouping of the differentially expressed (DE) genes according to biological functions revealed the involvement of processes such as ‘embryonic and organismal development’, ‘organ morphology’, ‘organ and tissue development’, ‘reproductive system development and function’. Molecular pathways that were altered were ‘amino acid metabolism’, ‘molecular transport’, ‘small molecule biochemistry’, ‘cell death and survival’, ‘cell-to-cell signaling and interaction’, ‘carbohydrate metabolism’ and ‘protein synthesis’. In conclusion, the present results demonstrated for the first time that prenatal protein undernutrition by albumen removal leads to long-term alterations of the hepatic transcriptome in the chicken. Overall design: 3 biological replicates per group (control, sham, albumen-deprived) were analyzed
Differential Expression of Genes and DNA Methylation associated with Prenatal Protein Undernutrition by Albumen Removal in an avian model.
Cell line, Subject
View SamplesIn this study we aimed to identify a baseline intrahepatic transcriptional signature associated with response in chronic hepatitis B patients treated with peginterferon-alfa-2a (peg-IFN) and adefovir.
An intrahepatic transcriptional signature of enhanced immune activity predicts response to peginterferon in chronic hepatitis B.
Specimen part, Disease, Disease stage
View SamplesCone photoreceptors are specialised sensory retinal neurons responsible for photopic vision, colour perception and visual acuity. Retinal degenerative diseases are a heterogeneous group of eye diseases in which the most severe vision loss typically arises from cone photoreceptor dysfunction or degeneration. Establishing a method to purify cone photoreceptors from retinal tissue can accelerate the identification of key molecular determinants that underlie cone photoreceptor development, survival and function. The work herein describes a new method to purify enhanced green fluorescent protein (EGFP)-labelled cone photoreceptors from adult retina of Tg(3.2TCP:EGFP) zebrafish. Electropherograms confirmed downstream isolation of high-quality RNA with RNA integrity number (RIN) >7.6 and RNA concentration >5.7 ng/l obtained from both populations. Reverse Transcriptase-PCR (RT-PCR) confirmed that the EGFP-positive cell populations express known genetic markers of cone photoreceptors that were not expressed in the EGFP-negative cell population. This work is an important step towards the identification of cone photoreceptor-enriched genes, protein and signalling networks responsible for their development, survival and function. In addition, this advancement facilitates the identification of novel candidate genes for inherited human blindness.
HDAC6 inhibition by tubastatin A is protective against oxidative stress in a photoreceptor cell line and restores visual function in a zebrafish model of inherited blindness.
Specimen part
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