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SRP066729
Homo sapiens
20 Downloadable Samples
NextSeq500
Description
Transcriptome profiling was performed on muscle biopsies from patients immediately before Total Knee Arthroplasty and two hours after TKA and tourniquet application. Overall design: RNA was isolated from 10 patients who were give vastus lateralis muscle biopsies immediately before surgery and 2 hours post surgery with tourniquet
Publication Title
Transcriptional profiling and muscle cross-section analysis reveal signs of ischemia reperfusion injury following total knee arthroplasty with tourniquet.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Circular RNAs (circRNAs) are a class of noncoding RNAs produced by a non-canonical form of alternative splicing called back-splicing. To investigate a potential role of circRNAs in the p53 pathway, we analyzed RNA-seq data from colorectal cancer cell lines (HCT116, RKO and SW48) in the presence or absence of DNA damage. Surprisingly, unlike the strong p53-dependent induction of hundreds of p53-induced mRNAs, only a few circRNAs were induced from the p53-induced genes. Circ-MDM2, an annotated circRNA from the MDM2 locus, was one of the handful of circRNAs that originated from a p53-induced gene. Given the central role of MDM2 in suppressing p53 protein levels and p53 activity, we investigated the function of circ-MDM2. Knocking down circ-MDM2 with siRNAs that targeted the circ-MDM2 junction and had no effect on linear MDM2 mRNA, resulted in increased basal p53 levels and growth defects in vitro and in vivo. Consistent with these results, transcriptome profiling showed increased expression of several direct p53 targets, reduced Rb phosphorylation and defects in G1-S progression upon silencing circ-MDM2. Our results reveal the role of a novel circRNA by which the MDM2 locus suppresses p53 levels and cell cycle progression.
Publication Title
A Circular RNA from the <i>MDM2</i> Locus Controls Cell Cycle Progression by Suppressing p53 Levels.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In addition to the estrogen responsive element (ERE)-dependent gene expression, E2-ERbeta regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERbeta signaling is unclear. Our studies in infected ER-negative cell models with an ERbeta mutant (ERbetaDBD) that functions exclusively at the ERE-independent pathway demonstrated that genomic responses assessed by microarrays from the ERE-independent pathway to E2-ERbeta are not sufficient to alter cellular growth, death or motility. These findings suggest that the ERE-dependent pathway is the canonical E2-ERbeta signaling in model cell lines.
Publication Title
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In addition to the estrogen responsive element (ERE)-dependent gene expression, E2-ERalpha regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERalpha signaling is unclear. Our studies in infected ER-negative cell models with an ERalpha mutant (ERalpha 203/204/211E) that functions exclusively at the ERE-independent pathway demonstrated that genomic responses assessed by microarrays from the ERE-independent pathway to E2-ERalpha are not sufficient to alter cellular growth, death or motility. These findings suggest that the ERE-dependent pathway is the canonical E2-ERalpha signaling in model cell lines.
Publication Title
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In addition to the estrogen responsive element (ERE)-dependent gene expression, E2-ERalpha regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERalpha signaling is unclear. Our studies in infected ER-negative cell models with an ERalpha demonstrated that genomic responses assessed by microarrays from the alter cellular growth, death or motility.
Publication Title
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
To understand how haploinsufficiency of progranulin (PGRN) protein causes frontotemporal dementia (FTD), we created induced pluripotent stem cells (iPSC) from patients carrying the GRNIVS1+5G>C mutation (FTD-iPSCs). FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD and known to express PGRN. Although generation of neuroprogenitors was unaffected, their further differentiation into neurons, especially CTIP2-, FOXP2- or TBR1-TUJ1 double positive cortical neurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of PGRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNAseq analysis confirmed reversal of altered gene expression profile following genetic correction. Wnt signaling pathway, one of the top defective pathways in FTD-iPSC-derived neurons coupled with its reversal following genetic correction, makes it an important candidate. Therefore, we demonstrate for the first time that PGRN haploinsufficiency hampers corticogenesis in vitro. Overall design: We profiled 6 samples: two biological replicates for 3 conditions. Condition 1 consists of neuronal progeny derived from human Embryonic Stem Cells. Condition 2 consists of neuronal progeny derived from induced pluripotent stem cells generated from patients carrying PGRN mutation. Condition 3 consists of neuronal progeny derived from induced pluripotent stem cells generated from patients carrying PGRN mutation, genetically modified to correct the PGRN defect.
Publication Title
Restoration of progranulin expression rescues cortical neuron generation in an induced pluripotent stem cell model of frontotemporal dementia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The development of an effective therapy against tauopathies like Alzheimers disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The development of an effective therapy against tauopathies like Alzheimers disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Specimen part, Treatment
View Samples