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GSE35554
Mus musculus, Drosophila melanogaster, Homo sapiens
24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Drosophila melanogaster
- 17 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila, and mouse models, we show that the proteins encoded by SMARCAL1 orthologues localize to transcriptionally active chromatin and modulate gene expression. We also show that similar to SIOD patients, deficiency of the SMARCAL1 orthologues alone is insufficient to cause disease in fruit flies and mice although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD.
Publication Title
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina Genome Analyzer II
Description
Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila, and mouse models, we show that the proteins encoded by SMARCAL1 orthologues localize to transcriptionally active chromatin and modulate gene expression. We also show that similar to SIOD patients, deficiency of the SMARCAL1 orthologues alone is insufficient to cause disease in fruit flies and mice although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD. Overall design: The RNA sequencing libraries were constructed from the liver RNA of 3-4-month Smarcal1del/del and wt female mice (n=3/group) at 20°C and after 1 hour at 39.5°C. These libraries were sequenced using the whole transcriptome shotgun sequencing procedure.
Publication Title
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila, and mouse models, we show that the proteins encoded by SMARCAL1 orthologues localize to transcriptionally active chromatin and modulate gene expression. We also show that similar to SIOD patients, deficiency of the SMARCAL1 orthologues alone is insufficient to cause disease in fruit flies and mice although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD.
Publication Title
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Drosophila Gene 1.0 ST Array (drogene10st)
Description
Mitochondrial DNA (mtDNA) encodes essential components of the respiratory chain and loss of mtDNA leads to mitochondrial dysfunction and neurodegeneration. Mitochondrial transcription factor A (TFAM) is an essential component of mtDNA replication and a regulator of mitochondrial copy number in cells. Studies have shown that TFAM knockdown leads to mitochondrial dysfunction and respiratory chain deficiencies. ATP synthase is Complex V of the mitochondrial respiratory chain. It is driven by a proton gradient between the intermembrane space and the mitochondrial matrix and generates the majority of cellular ATP. The knockdown of coupling factor 6 (Cf6), one of the components of the proton channel F0, causes dysfunction in the complex, leading to mitochondrial dysfunction and respiratory chain deficiencies. Using gene expression analysis, we aimed to investigate the effects of mtDNA dysfunction in the CNS at the molecular level.
Publication Title
Mitochondrial retrograde signaling regulates neuronal function.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 80 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The etiology behind cancer-related fatigue (CRF) is currently unknown. The physiological mechanisms of CRF are based on limited evidence that genetic factors, energy expenditure, metabolism, aerobic capacity, and the individual's immune response to inflammation are responsible for the experience of CRF. Gene expression profiling using microarray analysis from white blood cells of men with non-metastatic prostate cancer shows significant, differential expression of 463 probesets during localized external beam radiation therapy (EBRT). Pathway analysis shows a central role of SNCA (alpha-synuclein gene) among these differentially expressed probesets. Significant expression of SNCA was confirmed by qPCR (p<.001) and ELISA (p<.001) over time during EBRT. A significant correlation was noted between averaged fatigue scores and delta CT values of SNCA expression using confirmatory qPCR over time during EBRT (R=-.90, p=.006). Development of fatigue experienced by these men during EBRT may be mediated by SNCA expression. Pathways related to alpha-synuclein may serve as useful biomarkers to understand the mechanisms behind the development of fatigue.
Publication Title
Upregulation of α-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Mus musculus
- 27 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2500
Description
An improved understanding of the anti-tumor CD8+ T cell response after checkpoint blockade would enable more informed and effective therapeutic strategies. Here we examined the dynamics of the effector response of CD8+ tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8+ TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1? TILs. These cells could be divided into subsets bearing characterstics of naive-, effector-, and memory-precursor-like cells. Effector- and memory-precursor-like TILs contained tumor-antigen-specific cells, exhibited proliferative and effector capacity, and expanded in response to different checkpoint blockade therapies across different tumor models. The memory-precursor-like subset shared features with CD8+ T cells associated with response to checkpoint blockade in patients and was compromised in the absence of Tcf7. Expression of Tcf7 was requisite for the efficacy of diverse immunotherapies, highlighting the importance of this transcriptional regulator in the development of effective CD8+ T cell responses upon immunotherapy. Overall design: (i) RNAseq of Wild Type Naïve-like, Memory-like and Effector-like subpopulations of PD1-CD8+ Tumor infiltrating lymphocytes isolated from MC38-OVA. CD62LhiSlamf7-CX3CR1-, CD62L-Slamf7hiCX3CR1- and CD62L-Slamf7hiCX3CR1+ subsets within PD-1-CD8+ TILs (ii) RNAseq from WT mice, Tim-3+PD-1+ and Tim-3-PD-1- CD8+ TILs were isolated by cell sorting from MC38-OVA tumor-bearing mice that were treated with anti-PD-1 and anti-Tim-3 antibodies or isotype controls. (iii) Droplet-based single-cell RNA-Seq of Tim-3-PD-1- CD8+ TILs from MC38-OVA tumor-bearing WT mice that were treated with anti-PD-1 and anti-Tim-3 antibodies or isotype controls.
Publication Title
Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1<sup>-</sup>CD8<sup>+</sup> Tumor-Infiltrating T Cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumors from pancreatic cancer specimens obtained at surgery were used for efficacy testing and biologic analysis
Publication Title
Coordinated epidermal growth factor receptor pathway gene overexpression predicts epidermal growth factor receptor inhibitor sensitivity in pancreatic cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
We report the transcriptional changes in Drosophila after administration of Actin or buffer control Overall design: Examination of transcriptional responses to actin versus buffer injected flies at 3,6 and 24 hours post injection (each time point includes triplicate samples)
Publication Title
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in <i>Drosophila melanogaster</i>.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression data from 21 triple negative breast cancer samples treated with cisplatin & bevacizumab in the neoadjuvant setting as part of a clinical trial.
Publication Title
Overexpression of BLM promotes DNA damage and increased sensitivity to platinum salts in triple-negative breast and serous ovarian cancers.
Sample Metadata Fields
Specimen part
View Samples