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SRP042228
Homo sapiens
322 Downloadable Samples
IlluminaHiSeq2000
Description
We report the global pattern of ileal gene expression in a cohort of 359 treatment-naïve pediatric Crohn Disease, Ulcerative Colitis patients and controls. We focus on genes with consistent altered expression in inflamed and unaffected ileum of CD [ileal-involved CD (iCD) and non-invloved ileal CD (cCD)], but not in the ileum of ulcerative colitis or control. Overall design: Ileal biopsies were obtained during diagnostic colonoscopies of children and adolescents aged less than 17 years, who presented with IBD-like symptoms. All patients underwent baseline colonoscopy and histological characterization; non-IBD controls were those with suspected IBD, but with no microscopic or macroscopic inflammation and normal radiographic, endoscopic, and histologic findings. Biopsies were stored at -80 degrees.
Publication Title
Defining the Celiac Disease Transcriptome using Clinical Pathology Specimens Reveals Biologic Pathways and Supports Diagnosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this experiments different treatments were applied to lung cancer cell lines
Publication Title
Ingenuity network-assisted transcription profiling: Identification of a new pharmacologic mechanism for MK886.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 135 Downloadable Samples
- NextSeq 500
Description
Multiple myeloma (MM), a plasma cell (PC) malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity within and between patients is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA-seq to study the heterogeneity of 40 individuals along the MM progression spectrum. We define malignant PC at single cell resolution, demonstrating high inter-patient variability that can be explained by expression of known MM drivers and additional putative factors. Within newly diagnosed patients, we identify extensive sub-clonal structures for 10/29 patients. In asymptomatic patients with early disease and in minimal residual disease post-treatment, we detect tumor PC for a subset of the patients, with the same drivers of active myeloma. Single cell analysis of rare circulating tumor cells (CTC) allows detection of malignant PC, which reflect the BM disease. Our work establishes scRNA-seq for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients. Overall design: The study includes 29 newly diagnosed patients with plasma cell neoplasms and 11 control donors, for which bone marrow plasma cells were single cell sorted by FACS, and their mRNA sequenced. For 11 patients, targeted genomic DNA panel analysis for myeloma was performed.
Publication Title
Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Glioblastomas grow in a rich neurochemical mileu, but targeting neurochemical signaling as a potential therapeutic avenue for these incurable tumors has been underexplored. Thus, we probed patient derived glioblastoma stem cells with a focused library of neurochemicals, to identify new therapeutic targets. Dopaminergic, serotonergic and cholinergic pathways were found to be active against glioblastoma. In particular, dopamine receptor D4 (DRD4) antagonists selectively inhibited glioblastoma growth in vitro and in vivo, in addition to showing synergistic effect with temozolomide. Small molecule or genetic antagonism of DRD4 suppressed ERK1/2 signaling and impaired autophagic flux causing accumulation of autophagic vacuoles and ubiquitinated proteins, associated with G0/G1 cell cycle arrest. These data suggest a new mechanism for treating glioblastoma through modulating dopamine DRD4 signaling.
Publication Title
Inhibition of Dopamine Receptor D4 Impedes Autophagic Flux, Proliferation, and Survival of Glioblastoma Stem Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Objective: Long non-coding RNAs (lncRNA) regulate gene transcription and diverse cellular functions. We previously defined a novel core inflammatory and metabolic ileal gene signature in treatment naïve pediatric Crohn Disease (CD), however, genome-wide characterization of lncRNA expression was lacking. We now extend our analyses to define a more comprehensive view that includes lncRNA. Design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 177 ileal biopsies. Co-expression analysis was used to identify functions and tissue-specific expression. RT-PCR was used to test lncRNAs regulation by IL-1ß in Caco-2 enterocytes model. Results: We characterize a widespread dysregulation of 459 lncRNA in the ileum of treatment naïve pediatric CD patients. Unsupervised and supervised classifications using the 459 lncRNA showed comparable patients' grouping as the 2160 dysregulated protein-coding genes, linking lncRNA to CD pathogenesis. Co-expression and functional annotation enrichment analyses across several tissues and cell types showed that the up-regulated LINC01272 is associated with a myeloid pro-inflammatory signature while the down-regulated HNF4A-AS1 exhibits association with an epithelial metabolic signature. We further validated expression and regulation of prioritized lncRNA upon IL-1ß exposure in differentiated Caco-2 cells. Finally, we identified significant correlations between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury. Conclusion: We define differentially expressed lncRNA in the ileum of treatment naive pediatric CD. We show lncRNA utility to correctly classify disease or healthy states and demonstrate their regulation in response to an inflammatory signal. These lncRNA, after mechanistic exploration, may serve as potential new targets for RNA-based interventions. Overall design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 21 days differentiated caco-2 cells
Publication Title
Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Specific vulnerability of neurons in the human entorhinal cortex has been associated with the onset of disease.
Publication Title
Differential gene expression analysis of human entorhinal cortex support a possible role of some extracellular matrix proteins in the onset of Alzheimer disease.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Teratoma formation is the gold standard assay for testing the capacity of human stem cells to differentiate into all embryonic germ layers. Although widely used, little effort has been made to transform this qualitative assay into a quantitative one. Using gene expression data from a wide variety of cells, we created a gene scorecard representing tissues from all three germ layers as well as an extraembryonic tissue. A calculated grade using this gene list successfully distinguishes pluripotent stem cell-initiated teratomas from malignant tumors, thereby translating cell potency into a quantitative measure. This new methodology, named TeratoScore, thus assesses the pluripotency of human cells, and is easily performed using an open-source code. The new teratoma database also allowed us to examine the gene expression differences between tumors with a diploid karyotype and those initiated by aneuploid cells. We found that while teratomas originating from aneuploid cells pass the TeratoScore benchmark for pluripotency, they exhibit aberrant gene expression congruent with human chromosomal syndromes (such as Down syndrome). This gene expression signature is significantly different from that of teratomas originating from diploid cells, particularly in central nervous system-specific genes, suggesting aberrant teratomas may be beneficial for in vivo disease modeling. Teratoma formation followed by TeratoScore analysis can rapidly assess cell potency and allows comparison between different pluripotent cell lines.
Publication Title
TeratoScore: Assessing the Differentiation Potential of Human Pluripotent Stem Cells by Quantitative Expression Analysis of Teratomas.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Only a minority of medulloblastoma cells can self-renew and sustain tumor growth. In the Patched1+/- mouse model, these cells are quiescent and express the stem cell marker Sox2. We sought to define the gene expression profiling of these cells to gain insight into the molecular pathways that govern this population.
Publication Title
Quiescent sox2(+) cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 384 Downloadable Samples
- Illumina HiSeq 2500
Description
The interaction between a pathogen and a host is a highly dynamic process in which both agents activate complex programs. Here, we introduce a single-cell RNA-Seq method (scDual-Seq) that simultaneously captures both host and pathogen transcriptomes and use it to study the process of infection of individual mouse macrophages with the intracellular pathogen Salmonella typhimurium. Among the infected macrophages, we found three subpopulations and we show evidence for a linear progression through these subpopulations, supporting a model in which these three states correspond to consecutive stages of infection. Overall design: 96 single cells in 4 time point of infection (0,2.5,4,8 hours after infection)
Publication Title
scDual-Seq: mapping the gene regulatory program of Salmonella infection by host and pathogen single-cell RNA-sequencing.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Mus musculus
- 96 Downloadable Samples
- Illumina HiSeq 2500
Description
The interaction between a pathogen and a host is a highly dynamic process in which both agents activate complex programs. Here, we introduce a single-cell RNA-Seq method (scDual-Seq) that simultaneously captures both host and pathogen transcriptomes and use it to study the process of infection of individual mouse macrophages with the intracellular pathogen Salmonella typhimurium. Among the infected macrophages, we found three subpopulations and we show evidence for a linear progression through these subpopulations, supporting a model in which these three states correspond to consecutive stages of infection. Overall design: 40 single cells, 6 ten cells bulk, 2 hundred cells bulk, in two time point of infection (0,4 hours after infection)
Publication Title
scDual-Seq: mapping the gene regulatory program of Salmonella infection by host and pathogen single-cell RNA-sequencing.
Sample Metadata Fields
Cell line, Subject, Time
View Samples