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 SamplesLittle is known about the early transcriptional events in innate immune signaling in immature and tolerogenic monocyte-derived dendritic cells (DCs), the professional antigen-presenting cells of our immune system. TLR ligands usually induce a proinflammatory transcriptional response, whereas IL10 and/or dexamethasone induce a more tolerogenic phenotype.
MicroRNA genes preferentially expressed in dendritic cells contain sites for conserved transcription factor binding motifs in their promoters.
Specimen part
View SamplesMicroglia, the resident immune cells of the central nervous system (CNS), have two distinct phenotypes in the developing brain: amoeboid form, known to be amoeboid microglial cells (AMC) and ramified form, known to be ramified microglial cells (RMC) alongside several intermediate forms. The AMC are characterized by being proliferative, phagocytic and migratory whereas the RMC are quiescent and exhibit a slow turnover rate. The AMC transform into RMC with advancing age, and this transformation is indicative of the gradual shift in the microglial functions. Both AMC and RMC respond to CNS inflammation, and they become hypertrophic when they are activated by trauma, infection or neurodegenerative stimuli. The molecular mechanisms and functional significance of morphological transformation of microglia during normal development and in disease conditions is not clear. It is hypothesized that AMC and RMC are functionally regulated by a specific set of genes encoding various signaling molecules and transcription factors. To address this, we carried out cDNA microarray analysis using lectin-labeled AMC and RMC isolated from frozen tissue sections of the corpus callosum of 5-day and 4-week old rat brain respectively, by laser capture microdissection (LCM). The global gene expression profiles of both microglial phenotypes were compared and the differentially expressed genes in AMC and RMC were clustered based on their functional annotations. This genome wide comparative analysis helps in identifying genes that are specific to AMC and RMC. The novel and specific molecules identified in both microglial phenotypes can be targeted for therapeutic purposes in developing and adult brain diseases.
Transcriptome analysis of amoeboid and ramified microglia isolated from the corpus callosum of rat brain.
Specimen part
View SamplesGENES ASSOCIATED WITH THE CELL CYCLE, LINEAGE COMMITMENT AND IMMUNOMODULATORY POTENTIAL DISCRIMINATE HUMAN POSTNATAL STEM CELLS OF DIFFERENT ORIGIN.
Functional differences between mesenchymal stem cell populations are reflected by their transcriptome.
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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 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 Samples