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Homo sapiens
24 Downloadable Samples
NextSeq 500
Description
Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was confirmed using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 expression without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to separate stem and progenitor cells, RNA-seq identified unique gene signatures for the separate populations which may serve as biomarkers. Pathways enrichment in stem cells identified ribosome biogenesis and membrane estrogen-receptor signaling with NF?B signaling enriched in progenitors and these were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified cancer stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Overall design: Comparing RNA-seq gene profiles in label-retaining prostate stem cells and non-retaining progenitor cells
Publication Title
Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Inherited genetic risk factors play an important role in cancer. However, other than cancer susceptibility genes found in familial cancer syndromes and inherited in a Mendelian fashion, little is known about modifier genes (germline variants that interact with each other and with environmental factors) that contribute to individual susceptibility. Here we develop a strategy parental strain expression mapping (PSEM), which utilizes the homogeneity of inbred mice and genome-wide mRNA expression analyses, to directly identify candidate germline modifier genes and pathways underlying phenotypic differences among murine strains exposed to transgenic activation of AKT1. We identified multiple candidate modifier pathways and specifically, the glycolysis pathway as a candidate negative modulator of AKT1-induced proliferation. In keeping with findings in murine models, the expression of the glycolysis pathway was strongly enriched in the non-cancer prostate tissue from patients with prostate cancer who did not recur after surgical resection. Together these data suggest that PSEM can directly identify germline modifier pathways of relevance to human disease.
Publication Title
Identification of prostate cancer modifier pathways using parental strain expression mapping.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
To understand the role of LSD1 in B cell differentiation, mice with B cell conditional deletion of LSD1 were intravenously inoculated with LPS. After 3 days, B220+GL7-CD138- naïve B cells and CD138+ plasmablasts were FACS-sorted from the spleens and RNA-seq was performed to identify LSD1-target regulated genes. Overall design: RNA-seq on control or LSD1-deficient murine naïve B cells or plasmablasts.
Publication Title
The Histone Demethylase LSD1 Regulates B Cell Proliferation and Plasmablast Differentiation.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples
SRP082964- Homo sapiens
- 5 Downloadable Samples
- Illumina HiSeq 2500
Description
Osteosarcoma (OS) is one of the most aggressive bone malignancy. Sub-optimal therapy has irretrievably compromised chances of survival of OS patients for years. Also lack of extensive research on this rare disease has hindered its therapeutic development. Cisplatin (CDDP) is an integral part of current treatment regime for OS. However, despite the proven benefits of CDDP, acquisition of resistance impedes therapy. Also, the molecular effects post CDDP insult in OS cells is poorly understood. Hence, we characterized molecular alterations associated with CDDP-exposure and resistance in OS cells. Resistance to CDDP in OS cells was developed and deep sequencing of mRNA was performed. It depicted an altered transcriptomic signature of resistant cells with enrichment of pathways regulating proliferation. Overall, a significant up-regulation of coding-RNAs and down-regulation of non-coding-RNAs were obtained. Further, analysis of immediate effect of CDDP-shock showed an increase in autophagy and JNK signaling, acting as a pro-survival strategy. Regulatory connections between MAPK signaling and autophagy favoring survival under CDDP-shock was elucidated. Taken together, this is the first study portraying not only global transcriptomic alterations in resistant OS cells but also showing key molecular changes associated with CDDP-insult in OS cells. Our results can be better utilized for future therapeutic benefit. Overall design: We analyzed 5 samples, each being the representative of stages in the acquisition of chemoresistance. Control was the parental HOS cell line with which other comparisons are/will be made in future.
Publication Title
Transcriptomic analysis associated with reversal of cisplatin sensitivity in drug resistant osteosarcoma cells after a drug holiday.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
E15.5 embryos were micro-disscted from Gata4 G295S mutant mice and littermate controls, RNA was isolated using Norgen total RNA isolation, and libraries were generated with the RNA TruSeq Stranded Total RNA kit. 50 base pair paired end reads were obtained on an illumina high seq 2500. Fastq files were aligned to the mouse genome using STAR aligner. QC was performed using RNASeQC and RSeQC. BAM files were processed using cufflinks pipeline. Overall design: The project aims to assess the differential gene expression at E15.5 between the outflow tracts of Gata4 G295S mutant embryos and wildtype littermate controls.
Publication Title
Developmental origins for semilunar valve stenosis identified in mice harboring congenital heart disease-associated <i>GATA4</i> mutation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of patients taking statins experience muscle related adverse events. Myalgia, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels, is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin-associated myalgia are not clearly understood. To elucidate changes in gene expression associated with statin-induced myalgia, we compared profiles of gene expression in the biopsied skeletal muscle from statin-intolerant patients undergoing statin re-challenge versus those of statin-tolerant controls. A robust separation of statin-intolerant and statin-tolerant cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of statin intolerant patients, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals are genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario further bolstered by the discovery that a number of single nucleotide polymorphisms (e.g., SLCO1B1, SLCO2B1 and RYR2) associated with statin myopathy were observed with increased frequency among statin-intolerant study subjects.
Publication Title
Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
MicroRNAs have emerged as key regulators of B cell fate decisions and immune function. Deregulation of several microRNAs in B cells leads to the development of autoimmune disease and cancer in mice. We demonstrate that the microRNA-212/132 cluster (miR-212/132) is induced in B cells in response to B cell receptor signaling. Enforced expression of miR-132 results in a block in early B cell development at the pre-pro-B cell to pro-B cell transition and induces apoptosis in primary bone marrow B cells. Importantly, loss of miR-212/132 results in increased B cell output under non-homeostatic conditions. We find that miR-212/132 regulates B lymphopoiesis by targeting the transcription factor SOX4. Co-expression of SOX4 with miR-132 rescues the defect in B cell development from over-expression of miR-132 alone. In addition, we show that the expression of miR-132 in cells that are prone to spontaneous B cell cancers can have a protective effect on cancer development. We have thus uncovered a novel regulator of B cell lineage specification that may potential applications in B cell cancer therapy Overall design: RNA-seq of wild-type and microRNA-212/132 knock-out B-cells after IgM stimulation
Publication Title
The microRNA-212/132 cluster regulates B cell development by targeting Sox4.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Patients with bicuspid aortic valve (BAV) have increased risk of thoracic ascending aortic aneurysm (AscAA) and dissection compared to those with a normal tricuspid aortic valve (TAV). The present study was undertaken to evaluate whether differences in gene expression exist in aortas from BAV and TAV patients with AscAA.
Publication Title
Elevated expressions of osteopontin and tenascin C in ascending aortic aneurysms are associated with trileaflet aortic valves as compared with bicuspid aortic valves.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Knocking down ALKBH5 in Glioma Stem Cells resulted in an altered gene expression profile
Publication Title
m<sup>6</sup>A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of DZNep-induced gene expression changes in cultured podocytes. The hypothesis tested in the present study was that DZnep ultimately augments Txnip expression, increasing oxidative stress in podocytes. These results provide important information on the response of podocytes to histone methyltransferase inhibition and a possible mechanism for DZNep action in podocytes.
Publication Title
The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in Diabetes.
Sample Metadata Fields
Specimen part
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