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SRP053190
Homo sapiens
32 Downloadable Samples
IlluminaHiSeq2000
Description
Background: Transcription control of mitochondrial metabolism is essential for cellular function. A better understanding of this process will aid the elucidation of mitochondrial disorders, in particular of the many genetically unsolved cases of oxidative phosphorylation (OXPHOS) deficiency. Yet, to date only few studies have investigated nuclear gene regulation in the context of OXPHOS deficiency. In this study, we combined RNA sequencing of human complex I-deficient patient cells across 32 conditions of perturbed mitochondrial metabolism, with a comprehensive analysis of gene expression patterns, co-expression calculations and transcription factor binding sites. Results: Our analysis shows that OXPHOS genes have a significantly higher co-expression with each other than with other genes, including mitochondrial genes. We found no evidence for complex-specific mRNA expression regulation in the tested cell types and conditions: subunits of different OXPHOS complexes are similarly (co-)expressed and regulated by a common set of transcription factors. However, we did observe significant differences between the expression of OXPHOS complex subunits compared to assembly factors, suggesting divergent transcription programs. Furthermore, complex I co-expression calculations identified 684 genes with a likely role in OXPHOS biogenesis and function. Analysis of evolutionarily conserved transcription factor binding sites in the promoters of these genes revealed almost all known OXPHOS regulators (including GABP, NRF1/2, SP1, YY1, E-box factors) and a set of six yet uncharacterized candidate transcription factors (ELK1, KLF7, SP4, EHF, ZNF143, and EL2). Conclusions: OXPHOS genes share an expression program distinct from other mitochondrial genes, indicative of targeted regulation of this mitochondrial sub-process. Within the subset of OXPHOS genes we established a difference in expression between subunits and assembly factors. Most transcription regulators of genes that co-express with complex I are well-established factors for OXPHOS biogenesis. For the remaining six factors we here suggest for the first time a link with transcription regulation in OXPHOS deficiency. Overall design: RNA-SEQ of whole cell RNA in 2 control and 2 complex I deficient patient fibroblast cell lines treated with 4 compounds in duplicate, resulting in a total of 2x2x4x2=32 samples
Publication Title
Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Defective complex I (CI) is the most common type of oxidative phosphorylation (OXPHOS) disease in patients, with an incidence of 1 in 5,000 live births. Complex I deficiency can present in infancy or early adulthood and shows a wide variety of clinical manifestations, including Leigh syndrome, (cardio)myopathy, hypotonia, stroke, ataxia and lactic acidosis. A number of critical processes and factors, like superoxide production, calcium homeostasis, mitochondrial membrane potential and mitochondrial morphology, are known to be involved in clinical CI deficiency, but not all factors are yet known and a complete picture is lacking.
Publication Title
Transcriptional changes in OXPHOS complex I deficiency are related to anti-oxidant pathways and could explain the disturbed calcium homeostasis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Study on changes in gene expression in primary cultures of neonatal rat ventricular cardiomyocytes to electric stimulation.
Publication Title
Electrical signals affect the cardiomyocyte transcriptome independently of contraction.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- NextSeq 500
Description
Mutations in the RNA splicing complex member SRSF2 are found frequently in myelodysplastic syndrome and related malignancies such as chronic myelomonocytic leukemia. These mutations cluster on proline 95, with P95H the most frequent. How SRSF2P95H mutations modify hematopoiesis and promote MDS/MPN development is not clear. We have established a conditionally activatable Srsf2P95H/+ knock-in allele which, when expressed within the hematopoietic stem cell populations caused profound myeloid bias, at the expense of erythroid and lymphoid cells, and a reduced frequency and competitive repopulation of HSCs. Long-term aging of Srsf2P95H/+ resulted in the development of MDS/MPN characterised by myeloid dysplasia and monocytosis. Reproducible key phenotypic features make this a mouse model suitable for mechanistic and preclinical MDS sudies. Overall design: RNAseq of whole bone marrow in vivo tamoxifen treated R26CreERT2 Srsf2 P95H generated by deep sequencing, using Illumina NextSeq500
Publication Title
<i>Srsf2</i><i><sup>P95H</sup></i> initiates myeloid bias and myelodysplastic/myeloproliferative syndrome from hemopoietic stem cells.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Mesenchymal stromal cells (MSC) were isolated from human bone marrow. Here, we have compared gene expression profiles of MSC at early and late passages and upon stimulation with transforming growth factor beta 1 (TGF-b1). Stimulation was performed with 1ng/mL TGF-b1 for 1, 4, or 12 hours as indicated. The goal of this study was to determine if senescence-associated gene expression changes and TGF-b1 induced gene expression changes are related.
Publication Title
TGF-beta1 does not induce senescence of multipotent mesenchymal stromal cells and has similar effects in early and late passages.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play a central role. During active multiple sclerosis foamy macrophages and microglia, containing degenerated myelin, are abundantly found in demyelinated areas. Recent studies have described an altered macrophage phenotype after myelin internalization. However, by which mechanisms myelin affects the phenotype of macrophages and how this phenotype can influence lesion progression is unclear.
Publication Title
Myelin-derived lipids modulate macrophage activity by liver X receptor activation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 77 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
T lymphocytes are orchestrators of adaptive immunity. Nave T cells may differentiate into the Th1, Th2, Th17 or iTreg phenotype, depending on environmental co-stimulatory signals. In order to identify the genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli an pathway inhibitors
Publication Title
Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: We have previously shown that the Gene expression Grade Index (GGI) was able to identify two subtypes of estrogen receptor (ER)-positive tumors that were associated with statistically distinct clinical outcomes in both untreated and tamoxifen-treated patients. Here, we aim to investigate the ability of the GGI to predict relapses in postmenopausal women who were treated with tamoxifen (T) or letrozole (L) within the BIG 1-98 trial.
Publication Title
The Gene expression Grade Index: a potential predictor of relapse for endocrine-treated breast cancer patients in the BIG 1-98 trial.
Sample Metadata Fields
Age, Specimen part, Disease stage, Treatment
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Multipotent progenitors (MPP) and common dendritic cell progenitors (CDP) were obtained from mouse bone marrow, followed by in vitro culture with a specific cytokine cocktail and FACS sorting (Felker et al., 2010; Ser et al., 2012). Cells were treated with 10 ng/ml recombinant human TGF-1 (R&D Systems, Minneapolis, USA) for 2, 4, 8, 12 and 24 h as described (Felker et al., 2010) or left untreated.
Publication Title
TGF-β stimulation in human and murine cells reveals commonly affected biological processes and pathways at transcription level.
Sample Metadata Fields
Specimen part
View Samples