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SRP101737
Homo sapiens
33 Downloadable Samples
Illumina HiSeq 2500
Description
The goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age
Publication Title
Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Cancer progression is associated with alterations of epigenetic regulators such as histone-lysine demethylases 4 (KDM4)2-5. During breast cancer therapy, classical treatments fail to address resistant cancer stem cell populations6-10. Here, we identified a novel KDM4 inhibitor (KDM4(i)) with unique preclinical characteristics. KDM4(i) is a highly potent pan KDM4 inhibitor that specifically blocks the demethylase activity of KDM4A, B, C, and D but not that of the other members of the KDM family. We validated the KDM4(i) anti-tumoral properties under conditions recapitulating patient tumors. Therefore, we established a method to isolate and grow triple-negative breast cancer stem cells (BCSCs) from individual patient tumors after neoadjuvant chemotherapy. Limiting dilution orthotopic xenografts of these BCSCs faithfully regenerate original patient tumor histology and gene expression. KDM4(i) blocks proliferation, sphere formation and xenograft tumor growth of BCSCs. Importantly, KDM4(i) abrogates expression of EGFR, a driver of therapy-resistant triple-negative breast tumor cells11, via inhibition of the KDM4A demethylase activity. Taken together, we present a unique BCSC culture system as a basis for therapeutic compound identification and demonstrate that KDM4 inhibition is a new therapeutic strategy for the treatment of triple-negative breast cancer.
Publication Title
KDM4 Inhibition Targets Breast Cancer Stem-like Cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
An understanding of the mechanisms regulating white adipose tissue (WAT) formation is key for developing of new tools to treat obesity and its related diseases. Here, we identify DEPTOR as a positive regulator of adipogenesis whose expression is associated with obesity. In a polygenic mouse model of obesity/leanness, Deptor is part of the Fob3a QTL linked to obesity and we fine that Deptor is the highest priority candidate gene regulating WAT accumulation in this model. Using a doxycycline-inducible mouse model for Deptor overexpression, we confirmed that Deptor promotes WAT expansion in vivo. DEPTOR expression is elevated in WAT of obese humans and strongly correlates with the degree of obesity. We show that DEPTOR is induced during adipogenesis and that its overexpression cell-autonomously promotes, while its suppression blocks, adipogenesis. DEPTOR positively regulates adipogenesis by promoting the activity of the pro-adipogenic factors Akt/PKB and PPAR-gamma. These results establish DEPTOR as a physiological regulator of adipogenesis and provide new insights into the molecular mechanisms controlling WAT formation.
Publication Title
DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated with obesity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2000
Description
During chronic stimulation T cells acquire an exhausted phenotype characterized by expression of multiple inhibitory receptors and down-modulation of effector function. While this is required for the protection of the organism from excessive immunopathology, it also prevents successful immunity against persistent viruses or tumor cells. Here we demonstrate that CD8+ T cell exhaustion is characterized by a progressive decline in cellular metabolism. Exhausted T cells exhibit reduced metabolic reserve, impaired fatty acid oxidation and production of mitochondrial reactive oxygen species (ROS). Blockade of inhibitory PD-1/PD-L1 signaling rescued mitochondrial biogenesis, oxidative phosphorylation and ROS production, which was required for efficient restoration of cellular expansion and effector function. Expression of inhibitory receptors and impaired metabolic function was fuled by high amounts of IRF4, BATF and NFAT, which formed a TCR-responsive transcriptional circuit that sustained the transcriptional network responsible for T cell exhaustion. Overall design: Transcriptional profiling of T cells in mice with chronic and acute infections using RNA sequencing
Publication Title
Transcription Factor IRF4 Promotes CD8<sup>+</sup> T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The study was completed to compare expression profiles of primary human beta cells (in the form of adult human islets), to the expression profile of hESC-derived beta-like cells. A HES3 line modified by homologous recombination to express GFP under the insulin promoter allowed us to FACS sort the hESC-derived cells into purified insulin-positive (presumably beta-like cells), and insulin-negative populations.
Publication Title
The functional and molecular characterisation of human embryonic stem cell-derived insulin-positive cells compared with adult pancreatic beta cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CMPF is elevated in diabetes and is associated with impaired insulin secretion. We used microarrays to determine the effect of CMPF on gene expression in isolated islets.
Publication Title
The furan fatty acid metabolite CMPF is elevated in diabetes and induces β cell dysfunction.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Xenopus laevis
- 8 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
Foregut organogenesis is regulated by inductive interactions between the endoderm and the adjacent mesoderm. We identified genes induced in the foregut progenitors by the adjacent mesoderm.
Publication Title
Sizzled-tolloid interactions maintain foregut progenitors by regulating fibronectin-dependent BMP signaling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Exposure to aristolochic acid (AA) is linked to kidney disease and urothelial cancer in humans. The major carcinogenic component of the AA plant extract is aristolochic acid I (AAI). The transcription factor p53 acts as a tumour suppressor and is frequently mutated in AA-induced tumours. Using a mouse model, we previously showed that Trp53 genotype impacts on AAI-induced nephrotoxicity in vivo (i.e. p53 protects from AAI-induced renal proximal tubular injury), but the underlying mechanism(s) involved remain to be further explored. In the present study, we investigated the impact of p53 on AAI-induced gene expression in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with 3.5 mg/kg body weight (bw) AAI daily for 6 days. The Clariom™ S Assay microarray was used to elucidate gene expression profiles in mouse kidneys after AAI treatment in order to identify potential mechanisms by which AAI drives renal injury in Trp53(-/-) kidneys. Principle component analysis and hierarchical clustering in Qlucore Omics Explorer showed that gene expression in AAI-exposed Trp53(+/+), Trp53(+/-) and Trp53(-/-) kidneys is treatment-dependent. However, gene expression profiles did not segregate in a clear-cut manner according to Trp53 genotype, hence further investigations were performed by pathway analysis with MetaCore™. Several pathways, such as those related to epithelial-to-mesenchymal transition, transcription of hypoxia-inducible factor 1 targets, renal injury and secretion of xenobiotics were significantly altered to varying degrees for AAI-exposed kidneys. The top ten up-regulated genes included cyclin-dependent kinase inhibitor 1a (Cdkn1a), a mediator of cell cycle arrest; and neutrophil gelatinase-associated lipocalin (Ngal), which has been shown to play a role in nephritis by promoting inflammation and apoptosis. Members of the solute carrier (Slc) family (i.e. Slc22a2, Slc22a6, Slc22a7, Slc22a8) were amongst the top ten down-regulated genes. Pathway analysis also identified genes that are uniquely affected by AAI treatment in Trp53(+/+), Trp53(+/-) and Trp53(-/-) kidneys. Apoptotic pathways were modulated in Trp53(+/+) kidneys; whereas oncogenic and pro-survival pathways were significantly altered for Trp53(+/-) and Trp53(-/-) kidneys, respectively. Microarray gene expression analysis identified significant toxicogenomic responses to AAI that give novel insights into its mechanism of nephrotoxicity. Alterations of biological processes by AAI in Trp53(+/+), Trp53(+/-) and Trp53(-/-) kidneys could explain the mechanisms by which p53 protects from or p53 loss drives AAI-induced renal injury in vivo.
Publication Title
The impact of p53 on aristolochic acid I-induced nephrotoxicity and DNA damage in vivo and in vitro.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina Genome Analyzer
Description
To understand CD8 effector T cell differentiation in more detial we have used transcriptional profiling of antigen-specific CD8 T cells deficient in Blimp1, IL-2ra, or both, or Tbet. We reveal a common program of effector differentiation regulated by cytokine signaling and the combined activities of Blimp1 and T-bet, indicating remarkable redundancy and specificity in the control of genes involved in the differentiation of effector T cells. Overall design: Bone marrow chimeric mice were generated containing congenically marked wildtype and mutant heamatopoietic cells. The mice were infected with primed with PR8 influenza virus. Six weeks later they were infected with the heterologous HKx31 influenza virus. Antigen-specific (NP366) positive CD8 T cells were sorted. RNA was exracted and RNA sequening performed.
Publication Title
A molecular threshold for effector CD8(+) T cell differentiation controlled by transcription factors Blimp-1 and T-bet.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
To understand the developing striatum, key genes during development were identified using microarray analsyis tha could be considered as marker of medium spiny neurons. The ages studied is at peak striatal neurogenesis.
Publication Title
FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples