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GSE26079
Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Results of knocking-down AREG expression in SUM-149 cells by lenitviral infection of shRNA vectors and measuring gene expression provides information as to what genes are regulated by AERG in inflammatory breast cancer cells.
Publication Title
Knock-down of amphiregulin inhibits cellular invasion in inflammatory breast cancer.
Sample Metadata Fields
Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Estrogen-Related Receptor alpha (ERR) is a nuclear receptor that acts principally as a regulator of metabolism processes particularly in tissues subjected to high-energy demand. Besides its implication in energy metabolism and mitochondrial biogenesis, ERR was recently associated with tumorigenesis. Notably, increased expression of ERR was noted in different cancerous tissues as breast, ovary and colon. However, supplemental studies are required to better understand the role of ERR in colon carcinoma.
Publication Title
ERRα metabolic nuclear receptor controls growth of colon cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
Aim: RNA binding proteins (RBPs) are emerging as critical regulators of gut homeostasis via post-transcriptional control of key growth and repair pathways. IMP1 (IGF2 mRNA Binding Protein 1) is ubiquitously expressed during embryonic development and Imp1 hypomorphic mice exhibit severe gut growth defects. In the present study, we investigated the mechanistic contribution of intestinal epithelial IMP1 to gut homeostasis and response to injury. Method: We evaluated IMP1 expression in patients with Crohn's disease followed by unbiased ribosome profiling in IMP1 knockout cells. Concurrently, we measured differences in histology and cytokine expression in mice with intestinal epithelial-specific Imp1 deletion (Imp1?IEC) following dextran sodium sulfate (DSS)- colitis. Based on ribosome profiling analysis, we evaluated changes in autophagy in Imp1?IEC mice as well as in silico and in vitro approaches to evaluate direct protein:RNA interactions. Finally, we analyzed the consequence of genetic deletion of Atg7 in Imp1?IEC mice using colitis and irradiation models. Results: IMP1 was robustly upregulated in Crohn's disease patients and Imp1 loss lessened DSS-colitis severity. Unbiased ribosome-profiling revealed that IMP1 may coordinate translation of multiple pathways important for intestinal homeostasis, including cell cycle and autophagy, which we verified by Western blotting. Mechanistically, we observed evidence for increased autophagy flux in Imp1?IEC mice, reinforced through in silico and biochemical analyses revealing direct binding of IMP1 to autophagy transcripts. Finally, we found genetic deletion of Atg7 reversed the phenotype observed in DSS- or irradiation-challenged Imp1?IEC mice. Conclusions: IMP1 acts as a post-transcriptional regulator of gut epithelial repair, in part through modulation of autophagy. This study highlights the need for examining post-transcriptional regulation as a critical mechanism in inflammatory bowel disease. Overall design: Ribosome-footprinting and RNA-seq samples from WT SW480 cells and IMP1-/- knockout cells
Publication Title
Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptomic analysis of FACS-sorted Pax7nGFP quiescent skeletal muscle satellite cells cells from young, and old mice. Results provide knowledge about the molecular mechanisms underlying age-related skeletal muscle satellite cells homeostasis.
Publication Title
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptomic analysis of FACS-sorted Pax7nGFP quiescent skeletal muscle satellite cells cells from old, and post-mortem mice. Results provide knowledge about the molecular mechanisms underlying age-related skeletal muscle satellite cells homeostasis.
Publication Title
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The major inducible 70 kDa heat shock protein (hsp70) is host protective in a mouse model of measles virus (MeV) brain infection. Transgenic constitutive expression of hsp70 in neurons, the primary target of MeV infection, abrogates neurovirulence in neonatal H-2d congenic C57BL/6 mice. A significant level of protection is retained after depletion of T lymphocytes, implicating innate immune mechanisms. Focus of the present work was to elucidate the basis for hsp70-dependent innate immunity using this model. Transcriptome analysis of brains from transgenic (TG) and non-transgenic (NT) mice 5 days after infection identified type 1 interferon (IFN) signaling and macrophage activation/antigen presentation as the main differences linked to survival. The pivotal role for type 1 IFN in hsp70-mediated protection was demonstrated in mice with a genetically disrupted type 1 IFN receptor (IFNAR-/-), where IFNAR-/- eliminated the difference in survival between TG and NT mice. Brain macrophages, not neurons, are the predominant source of type 1 IFN in the virus-infected brain, and in vitro studies provided a mechanistic basis by which MeV-infected neurons can induce IFN- in uninfected microglia in an hsp70-dependent manner. MeV infection induced extracellular release of hsp70 from mouse neuronal cells that constitutively express hsp70, and extracellular hsp70 induced IFN- transcription in mouse microglial cells through Toll-like receptors 2 and 4. Collectively, results support a novel axis of type 1 IFN-dependent antiviral immunity in the virus-infected brain that is driven by hsp70.
Publication Title
hsp70 and a novel axis of type I interferon-dependent antiviral immunity in the measles virus-infected brain.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The three-dimensional (3D) folding of the chromosomal fibre in the human interphase nucleus is an important, but poorly understood aspect of gene regulation. Especially basic principles of 3D chromatin and chromosome organisation are still elusive. In this paper, we quantitatively analyse the 3D structure of large parts of chromosomes 1 and 11 in the G1 nucleus of human cells and relate it to the human transcriptome map (HTM). Despite a considerable cell-to-cell variation, our results show that subchromosomal domains, which are highly expressed, are more decondensed, have a more irregular shape and are located in the nuclear interior compared to clusters of low expressed genes. These aspects of chromosome structure are shared by six different cell lines and therefore are independent of cell type specific differences in gene expression within the investigated domains. Systematic measurements show that there is little to no intermingling of chromatin from different parts of the same chromosome, indicating that the chromosomal fibre itself is a compact structure. Together, our results reveal several basic aspects of 3D chromosome architecture, which are related to genome function.
Publication Title
The three-dimensional structure of human interphase chromosomes is related to the transcriptome map.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Small molecule splicing modifiers have been extensively described which target the generic splicing machinery and thus have low target specificity. We have identified potent splicing modifiers with unprecedented high selectively, correcting the splicing deficit of the SMN2 (survival motor neuron 2) gene in Spinal Muscular Atrophy (SMA). Here we show that they directly bind to two sites of the SMN2 pre-mRNA, thereby stabilizing a novel ribonucleoprotein (RNP) complex in the SMN2 gene that is critical for the high target specificity of these small molecules over other genes. In addition to the therapeutic potential of these molecules for treatment of SMA, our work may have wide-ranging consequences for further research to identify small molecules that target splicing correction of specific genes by interacting with tertiary RNA structures. Overall design: mRNA profiling of type I SMA fibroblasts treated with NVS-SM1
Publication Title
Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 79 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
The functional consequences of missense variants in disease genes are difficult to predict. We assessed if gene expression profiles could distinguish between BRCA1 or BRCA2 pathogenic truncating and missense mutation carriers and familial breast cancer cases whose disease was not attributable to BRCA1 or BRCA2 mutations (BRCAX cases). 72 cell lines from affected women in high-risk breast-ovarian families were assayed after exposure to ionising irradiation, including 23 BRCA1 carriers, 22 BRCA2 carriers, and 27 BRCAX individuals. A subset of 10 BRCAX individuals carried rare BRCA1/2 sequence variants considered to be of low clinical significance (LCS). BRCA1 and BRCA2 mutation carriers had similar expression profiles, with some subclustering of missense mutation carriers. The majority of BRCAX individuals formed a distinct cluster, but BRCAX individuals with LCS variants had expression profiles similar to BRCA1/2 mutation carriers. Gaussian Process Classifier predicted BRCA1, BRCA2 and BRCAX status with a maximum of 62% accuracy, and prediction accuracy decreased with inclusion of BRCAX samples carrying an LCS variant, and inclusion of pathogenic missense carriers. Similarly, prediction of mutation status with gene lists derived using Support Vector Machines was good for BRCAX samples without an LCS variant (82-94%), poor for BRCAX with an LCS (40-50%), and improved for pathogenic BRCA1/2 mutation carriers when the gene list used for prediction was appropriate to mutation effect being tested (71-100%). This study indicates that mutation effect, and presence of rare variants possibly associated with a low risk of cancer, must be considered in the development of array-based assays of variant pathogenicity.
Publication Title
BRCA1 and BRCA2 missense variants of high and low clinical significance influence lymphoblastoid cell line post-irradiation gene expression.
Sample Metadata Fields
Sex, Age
View Samples