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SRP070776
Homo sapiens
28 Downloadable Samples
Illumina HiSeq 2500
Description
To determine the role of the cytokine activin A in the regulation of human T follicular helper (Tfh) cell gene program, we performed a transcriptomic analysis (RNA-seq) of human naïve CD4 T cells differentiated in vitro with activin A. The analysis of the gene expression profile driven by activin A, alone or in combination with IL-12 (a know regulator of human Tfh differentiation/function), revealed that activin A can regulate the expression of multiple molecules involved in the differentiation and/or function of human Tfh cells. Overall design: Human naïve CD4 T cells were isolated from fresh PBMCs of healthy control subjects by magnetic bead isolation. Purity was measured by FACS as percentage of CD4+CD45RA+ cells and was 95% or higher. Upon isolation, naïve CD4 T cells were stimulated with anti-CD3/CD28 coated beads in the presence of the following cytokine combinations: no exogenous cytokines (beads only), activin A, IL-12, activin A+IL-12, TGFb, TGFb +IL12. Following 5 days of in vitro culture, live CD4 T cells were FACS sorted and gene expression was analyzed by RNA-seq. Data are from independent donors.
Publication Title
Activin A programs the differentiation of human TFH cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 70 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st), Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Alternative splicing is a key event to human transcriptome and proteome diversity and complexity. Recent evidence suggests that pancreatic cancer might possess particular patterns of splice variation that influence the function of individual genes contributing to tumour progression in this disease. The identification of new pancreatic cancer-associated splice variants would offer opportunities for novel diagnostics and potentially also represent novel therapeutic targets.
Publication Title
A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Pluripotent stem cells are being actively studied as a cell source for regenerating damaged liver. For long term survival of engrafting cells in the body, not only do the cells have to execute liverspecific function but also withstand the physical strains and invading pathogens. The cellular innate immune system orchestrated by the interferon (IFN) pathway provides the first line of defense against pathogens. The objective of this study is to assess the innate immune function as well as to systematically profile the IFN-induced genes during hepatic differentiation of pluripotent stem cells. To address this objective, we derived endodermal cells (day 5 postdifferentiation), hepatoblast (day 15) and immature hepatocytes (day 21) from human embryonic stem cells (hESC). Day 5, 15 and 21 cells were stimulated with IFN-a and subjected to IFN pathway analysis. Transcriptome analysis was carried out by RNA sequencing. The results showed that the IFN-a treatment activated STAT-JAK pathway in differentiating cells. Transcriptome analysis indicated stage specific expression of classical and non-classical IFNstimulated genes (ISGs). Subsequent validation confirmed the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated hepatocytes upon IFN treatment. Hepatitis C virus replication in hESC-derived hepatic cells induced the expression of ISGs – LAMP3, ETV7, RASGRP3, and TRANK1. The hESC-derived hepatic cells contain intact innate system and can recognize invading pathogens. Besides assessing the tissue-specific functions for cell therapy applications, it may also be important to test the innate immune function of engrafting cells to ensure adequate defense against infections and improve graft survival. Overall design: 12 samples total, 4 samples in each time point (day 5, day 15, day 21). Each group of 4 within each time point has 2 control and 2 treatment samples in which the cells were stimulated with human interferon-alpha A (R and D Systems) at a concentration of 5000 IU for 6 hours.
Publication Title
Characterization of type I interferon pathway during hepatic differentiation of human pluripotent stem cells and hepatitis C virus infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
GM-CSF receptor- deficient (Csf2rb/ or KO) mice develop a lung disease identical to hereditary pulmonary alveolar proteinosis (hPAP) in humans with recessive CSF2RA or CSF2RB mutations that impair GM-CSF receptor function. We performed pulmonary macrophage transplantation (PMT) of bone marrow derived macrophages (BMDMs) without myeloablation in Csf2rb/mice. BMDMs were administered by endotracheal instillation into 2 month-old Csf2rb/ mice. Results demonstrated that PMT therapeutic of hPAP in Csf2rb/ mice was highly efficacious and durable. Alveolar macrophages were isolated by bronchoalveolar lavage one year after administration subjected to microarray analysis to determine the effects of PMT therapy on the global gene expression profile.
Publication Title
Pulmonary macrophage transplantation therapy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
H69M cells derive from H69 small cell lung cancer cells subjected to prolonged treatment with HGF. Among the whole population of cells, a subset of more fibroblastic cells was isolated (H69M-mesenchymal). In this experiment we compared expression profiles of both cell lines
Publication Title
Targeting epithelial-to-mesenchymal transition with Met inhibitors reverts chemoresistance in small cell lung cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mrhl is a non coding RNA identified from mouse chromosome 8. It is a 2.4kb poly adenylated, nuclear restricted RNA expressed in multiple tissues. The 2.4 kb RNA also undergoes a nuclear processing event mediated through Drosha that generates an 80nt intermediate RNA. This study was aimed at understanding the functiion of mrhl by silencing the mrhl RNA in the mouse spermatogonial cells using a pool of siRNAs targeted against the mrhl and analyse the global gene expression change using Affymetrix mouse expression array. The mRNAs that showed significant change in expression in mrhl siRNA treated cells against control were studied further for their biological significance with respect to mrhl silencing.
Publication Title
mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its protein partner Ddx5/p68 in mouse spermatogonial cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes: RET, VHL, NF1, and subunits B, C and D of succinate dehydrogenase (SDH). The proteins encoded by these multiple genes regulate distinct functions. To identify molecular interactions between the distinct pathways we performed expression profiling of a large cohort of pheochromocytomas. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1?. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1? activity in tumors.
Publication Title
A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 53 Downloadable Samples
- Illumina HiSeq 2000
Description
The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins TRX-2 and TRX-3 do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, SKN-1 transcriptional activity remains largely unaffected. Interestingly, RNA-Seq revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport and localization being most prevalent. However, one prominent lipase-related gene, lips-6, is highly up regulated upon loss of trx-1 in a skn-1-dependent manner. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. Overall design: Four samples were analyzed: Two nematode strains were analyzed, each under non-stressed and stressed (10mM NaAs) conditions
Publication Title
TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans.
Sample Metadata Fields
Disease, Cell line, Subject
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
- NextSeq 500
Description
We profiled how animals RNA expression changes in response to osmotic stress, how lin-45 mutants have an altered response to osmotic stress, and how maternal preconditioning at 300 mM NaCl modifies progeny response to 500 mM NaCl Overall design: Examination of total RNAseq at 50 mM NaCl, 500 mM NaCl, and 500 mM NaCl from maternally preconditioned animals
Publication Title
Insulin-like signalling to the maternal germline controls progeny response to osmotic stress.
Sample Metadata Fields
Subject, Time
View Samples