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SRP109826
Homo sapiens
6 Downloadable Samples
Illumina HiSeq 4000
Description
We performed transcriptome analysis of Human Aortic Endothelial Cells after siRNA mediated knockdown of MTHFD2. We identified MTHFD2 as a key driver for a gene cluster which integrates mitochondrial one-carbon metabolism, serine synthesizing enzymes as well as common amino acid and ER stress response genes. Overall design: Human Aortic Endothelial Cells were treated with three different siRNAs against MTHFD2 or scramble for 72 h
Publication Title
Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- NextSeq 500
Description
Background: Here, the role of a-ketoglutarate (aKG) in the epi-metabolic control of DNA demethylation has been investigated in therapeutically relevant cardiac mesenchymal cells (CMSCs) isolated from controls and type 2 diabetes donors. Methods & results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs). Whole heart genomic DNA analysis revealed iterative oxidative cytosine modification accumulation in mice exposed to high fat diet (HFD), injected with streptozotocin (STZ) or both in combination (STZ-HFD). In this context, untargeted and targeted metabolomics indicated an intracellular reduction of aKG synthesis in D-CMSCs and in the whole heart of HFD mice. This observation was paralleled by a compromised thymine DNA glycosylase (TDG) and ten eleven translocation protein 1 (TET1) association and function with TET1 relocating out of the nucleus. Molecular dynamics and mutational analyses showed that aKG binds TDG on Arg275 providing an enzymatic allosteric activation. As a consequence, the enzyme significantly increased its capacity to remove G/T nucleotide mismatched or 5fC. Accordingly, an exogenous source of aKG restored the DNA demethylation cycle by promoting TDG function, TET1 nuclear localization and TET/TDG association. TDG inactivation by CRISPR/Cas9 knockout or TET/TDG siRNA knockdown induced 5fC accumulation thus partially mimicking the diabetic epigenetic landscape in cells of non- diabetic origin. The novel compound (S)-2-[(2,6-dichlorobenzoyl)amino]succinic acid (AA6), identified as an inhibitor of aKG-dehydrogenase, increased the aKG level in D- CMSCs and in the heart of HFD mice eliciting DNA demethylation, glucose uptake and insulin response. Conclusions: In this report we established that diabetes may epigenetically modify and compromise function of therapeutically relevant cardiac mesenchymal cells. Restoring the epi-metabolic control of DNA demethylation cycle promises beneficial effects on cells compromised by environmental metabolic changes. Overall design: Human primary cardiac mesenchymal cells (CMSC) from 7 diabetic (D) and 7 non-diabetic (ND) donors were analyzed after few rounds of ex vivo expansion. RNA was isolated and sequenced.
Publication Title
Stable Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells From Type2 Diabetes Patients: Rescue by α-Ketoglutarate and TET-TDG Functional Reactivation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Macrophages are a heterogeneous cell type implicated in injury, repair, and fibrosis after AKI, but the macrophage population associated with each phase is unclear.results of this study in a renal ischemia-reperfusion injury model allow phenotype and function to be assigned to CD11b+/Ly6C+ monocyte/macrophage populations in the pathophysiology of disease after AKI.
Publication Title
Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 412 Downloadable Samples
- NextSeq 500
Description
Primary RNASeq data for progenitor, resident, and stimulated (C.alb, LPS, injury, APAP+ starved overnight and pIC) mononuclear phagocytes from fourteen organs. Overall design: RNASeq data for over 400 samples comprising of 130 populations submitted by 16 labs (both non-ImmGen and ImmGen labs) from 8 locations around the world for ImmGen OpenSource Mononuclear Project. Samples were sorted in these facilities using ImmGen's stringent ULI protocol and shipped to one location for library preparation and sequencing. Contributor: Immunological Genome Project Consortium
Publication Title
ImmGen report: sexual dimorphism in the immune system transcriptome.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 389 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The study consist of patients who presented at Memorial Sloan-Kettering Cancer Center with a colonic neoplasm between 1992 and 2004. Biological specimens used in this study include primary colon adenocarcinomas, adenomas, metastasis and corresponding normal mucosae.
Publication Title
Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 221 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
RNA expression data was generated as part of a colon cancer study. Samples were obtained from patients, including primary colon cancer, polyps, metastases, and matched normal mucosa (obtained from the margins of the resection). The RNA was extracted from tissue samples obtained from resections and hybridized to Affymetrix HG-U133 arrays. RNA expression data was also obtained for a few cell lines.
Publication Title
Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples- Mus musculus
- 190 Downloadable Samples
- NextSeq 500
Description
Primary RNA Seq data for 11 diverse immunocyte populations from male and female mice of varying ages stimulated with different dose of IFN and sequenced using ImmGen's standard ultra-low input RNA-seq pipeline Overall design: RNASeq data for 11 cell populations from male and female mice generated by ImmGen labs to study sexual differences in the immune system (companion ATACseq datasets are found in GSE100738). These mice comprised of varying ages, including 6-8weeks and 2- 20months old. In addition, mice were stimulated with 1K and 10K Type 1 interferon to understand sex specific responses. contributor: Immunological Genome Project Consortium
Publication Title
ImmGen report: sexual dimorphism in the immune system transcriptome.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Poly(A) RNA profiling upon Gld2 knockdown in cultured hippocampal neurons
Publication Title
Bidirectional control of mRNA translation and synaptic plasticity by the cytoplasmic polyadenylation complex.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 89 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
RATIONALE: Human rhinovirus infections cause colds and trigger exacerbations of lower airway diseases. OBJECTIVES: To define changes in gene expression profiles during in vivo rhinovirus infections. METHODS: Nasal epithelial scrapings were obtained before and during experimental rhinovirus infection, and gene expression was evaluated by microarray. Naturally acquired rhinovirus infections, cultured human epithelial cells, and short interfering RNA knockdown were used to further evaluate the role of viperin in rhinovirus infections. MEASUREMENTS AND MAIN RESULTS: Symptom scores and viral titers were measured in subjects inoculated with rhinovirus or sham control, and changes in gene expression were assessed 8 and 48 hours after inoculation. Real-time reverse transcription-polymerase chain reaction for viperin and rhinoviruses was used in naturally acquired infections, and viperin mRNA levels and viral titers were measured in cultured cells. Rhinovirus-induced changes in gene expression were not observed 8 hours after viral infection, but 11,887 gene transcripts were significantly altered in scrapings obtained 2 days postinoculation. Major groups of up-regulated genes included chemokines, signaling molecules, interferon-responsive genes, and antivirals. Viperin expression was further examined and also was increased in naturally acquired rhinovirus infections, as well as in cultured human epithelial cells infected with intact, but not replication-deficient, rhinovirus. Knockdown of viperin with short interfering RNA increased rhinovirus replication in infected epithelial cells. CONCLUSIONS: Rhinovirus infection significantly alters the expression of many genes associated with the immune response, including chemokines and antivirals. The data obtained provide insights into the host response to rhinovirus infection and identify potential novel targets for further evaluation.
Publication Title
Gene expression profiles during in vivo human rhinovirus infection: insights into the host response.
Sample Metadata Fields
No sample metadata fields
View Samples