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SRP071088
Homo sapiens
12 Downloadable Samples
IlluminaHiSeq4000, IlluminaHiSeq2000
Description
Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis, the final common pathway leading to cirrhosis and liver failure for nearly every cause of chronic liver disease. Activation of HSCs in response to injury represents the key step in hepatic fibrogenesis, and is characterized by a phenotypic change from a non-fibrogenic, quiescent HSC to a fibrogenic HSC myofibroblast that secretes extracellular matrix proteins responsible for the fibrotic scar. We developed a small molecule screen to identify compounds that revert fibrotic human HSC myofibroblasts to an inactive phenotype through the quantification of lipid droplets with fluorescent microscopy. Conditions were optimized in a 384-well format using culture in Matrigel as a positive control. We screened 1600 compounds and identified 30 small molecules that induce reversion to an inactive phenotype. Among the hits, we identified five tricyclic antidepressants (TCAs) and showed that this class of drugs also repressed ACTA2 and COL1A1 while promoting PPAR-gamma expression. RNA sequencing analysis implicated extracellular matrix proteins and the sphingolipid pathway as a target of the TCAs. Overall design: HSCs and HSCs stimulated with TGF-beta were treated with the TCA, nortriptyline or ethanol vehicle for 48 hours. RNA-seq was performed in duplicate for each condition
Publication Title
Tricyclic Antidepressants Promote Ceramide Accumulation to Regulate Collagen Production in Human Hepatic Stellate Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 115 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial disease of unknown cause. It remains impractical to conduct early diagnosis and predict IPF progression just based on gene expression information. Moreover, the relationship between gene expression and quantitative phenotypic value in IPF keeps controversial. To identify biomarkers to predict survival in IPF, we profiled protein-coding gene expression in peripheral blood mononuclear cells (PBMCs). We linked the gene expression level with the quantitative phenotypic variation in IPF, including diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC) percent predicted. In silico analyses on the expression profiles and quantitative phenotypic data allowed for the generation of a set of IPF molecular signature that predicted survival of IPF effectively.
Publication Title
Sphingosine-1-phosphate lyase is an endogenous suppressor of pulmonary fibrosis: role of S1P signalling and autophagy.
Sample Metadata Fields
Sex, Age, Disease, Race
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Clinically significant radiation-induced lung injury (RILI) is associated with significant morbidity and mortality and a common toxicity in patients administered thoracic radiotherapy. While the molecular etiology of RILI is poorly understood, we previously characterized a murine model of RILI in which alterations in lung endothelial barrier integrity surfaced as a potentially important pathobiologic event. In these studies, inhibition of HMG-CoA reductase activity (simvastatin) reduced murine RILI-associated lung inflammation and vascular leak and attenuated radiation-induced dysregulation of sphingolipid metabolic pathway genes identified by genome-wide lung gene expression profiling. In the present study, we test the hypothesis that sphingolipid signaling components serve as important modulators of RILI pathobiology and novel therapeutic targets. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to cumulative sphingosine-1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage (BAL) fluid and lung tissue following 25 Gy exposure (6 weeks). Moreover, genetically-engineered mice with either targeted deletion of SphK1 (SphK1-/-), or with reduced expression of selective members of the S1P receptor family (S1PR1+/-, S1PR2-/-, S1PR3-/-,), exhibited marked susceptibility to RILI-mediated lung inflammation. Finally, we assessed the efficacy of three potent vascular barrier-protective S1P analogues FTY720 (FTY), fTysiponate (fTyS) and SEW-2871 (SEW) in attenuating indices of RILI. The phosphonate analogue, fTyS, and to a lesser degree SEW, exhibited significant attenuation of RILI and RILI-induced gene dysregulation compared to control RILI-challenged mice (6 weeks). In contrast, FTY failed to significantly alter physiologic or genomic changes compared to RILI-challenged controls. Together, these results support the targeting of sphingolipid components as a novel and effective therapeutic strategy in RILI.
Publication Title
Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Targets of Retinoic Acid (RA) and 3,4-didehydroretinoic acid (ddRA) were identified in primary human epidermal keratinocytes grown in the presence of atRA or ddRA for 4 and 24 hours.
Publication Title
The effect of two endogenous retinoids on the mRNA expression profile in human primary keratinocytes, focusing on genes causing autosomal recessive congenital ichthyosis.
Sample Metadata Fields
Treatment
View Samples- Danio rerio
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
Purpose: using RNA-seq as a screening tool to determine candidate genes of interest within a genetically defined neural subpopulation in the zebrafish embryonic spinal cord. Results: The early embryonic spinal cord displays patterns of spontaneous activity that generate the earliest motor behavior in the zebrafish. We show the behavior and the neural activity to be inhibited by environmental levels of light. Since at these young ages the fish is blind, and since restricted illumination patterns on the trunk of the fish can elicit a photo-response, we hypothesized that the photo-inhibition is an intrinsic property of the active central pattern generator network within the spinal cord. We FACS-isolated cells from this network as well as those from a panneuronal population and sequenced mRNAs. Through differential expression analysis we identified vertebrate ancient long opsin a as a candidate and then further validated its function in the circuit through knockdown and rescue experiments. Overall design: RNA sequencing of 2 FACS purified neural populations from zebrafish spinal cord.
Publication Title
A spinal opsin controls early neural activity and drives a behavioral light response.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Purpose: CEBPA mutations are found as either biallelic (biCEBPA) or monoallelic (moCEBPA). We set out to explore whether the kind of CEBPA mutation is of prognostic relevance in cytogenetically normal AML (CN-AML).
Publication Title
Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The adaptor protein Lnk is an important negative regulator of HSC homeostasis and self-renewal. This study aims to investigate the role of Lnk in HSC aging. Here we performed expression profiling of bone marrow CD150+CD48-LSK LT-HSCs from young and old WT and Lnk-/- mice. Results identify select Lnk-mediated pathways with potential involvement in HSC self-renewal and aging.
Publication Title
Lnk deficiency partially mitigates hematopoietic stem cell aging.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
THREE INDEPENDENT REPLICATES AND ARE THE CONTROL NON-INFECTED CELLS:
Publication Title
Modulation of NB4 promyelocytic leukemic cell machinery by Anaplasma phagocytophilum.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recessive retinitis pigmentosa (RP) is often caused by nonsense mutations that lead to low mRNA levels as a result of nonsense-mediated decay. Some RP genes are expressed at detectable levels in leukocytes as well as in the retina. We designed a microarray-based method to find recessive RP genes based on low lymphoblast mRNA expression levels
Publication Title
Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cancer cell phenotypes are partially determined by epigenetic specifications such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations. Here, we analyzed genome wide DNA methylation changes that were associated with pro-metastatic phenotypes in non-small cell lung cancer with Reduced Representation Bisulfite Sequencing. DNMT-inhibition by 5-Azacytidine at low concentrations reverted the pro-metastatic phenotype. 5-Azacytidine led to preferential loss of DNA methylation at sites that were DNA hypermethylated during the in vivo selection. Changes in DNA methylation persisted over time.
Publication Title
DNA methyltransferase inhibition reverses epigenetically embedded phenotypes in lung cancer preferentially affecting polycomb target genes.
Sample Metadata Fields
Cell line
View Samples