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GSE26386
Homo sapiens
19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf
Publication Title
Mapping and analysis of chromatin state dynamics in nine human cell types.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chromatin profiling has emerged as a powerful means for annotating genomic elements and detecting regulatory activity. Here we generate and analyze a compendium of epigenomic maps for nine chromatin marks across nine cell types, in order to systematically characterize cis-regulatory elements, their cell type-specificities, and their functional interactions. We first identify recurrent combinations of histone modifications and use them to annotate diverse regulatory elements including promoters, enhancers, transcripts and insulators in each cell type. We next characterize the dynamics of these elements, revealing meaningful patterns of activity for promoter states and exquisite cell type-selectivity for enhancer states. We define multi-cell activity profiles that reflect the patterns of enhancer state activity across cell types, as well as analogous profiles for gene expression, regulatory motif enrichments, and expression of the corresponding regulators. We use correlations between these profiles to link enhancers to putative target genes, to infer cell type-specific activators and repressors, and to predict and validate functional regulator binding motifs in specific chromatin states. These functional annotations and regulatory predictions enable us to revisit intergenic single-nucleotide polymorphisms (SNPs) associated with human disease in genome-wide association studies (GWAS). We find that for several diseases, top-scoring SNPs are precisely positioned within enhancer elements specifically active in relevant cell types. In several cases a disease variant affects a motif instance for one of the predicted causal regulators, thus providing a potential mechanistic explanation for the disease association. Our study presents a general framework for applying multi-cell chromatin state analysis to decipher cis-regulatory connections and their role in health and disease.
Publication Title
Mapping and analysis of chromatin state dynamics in nine human cell types.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of lung CD11c+ antigen presenting cells (APCs) isolated from wildtype or Mir22-/- mice exposed to nanoparticulate carbon black (nCB) for one month. MiR-22 plays important roles in nCB induced experimental emphysema through regulating APC activation. Results provide insight into the biological role and target genes of miR-22.
Publication Title
The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell-dependent emphysema.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
mRNA microarray analysis of bone marrow derived macrophages treated under four conditions, including Nave (N). Bone marrow derived macrophages (BMDM) were derived from the bone marrow of mice and cultured in the presence of PAO, IFN-gamma, or lipopolysaccharide (LPS). Profiled groups include Naive, LPS, IFN, PAO.
Publication Title
Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Although expansion of a polyglutamine tract in ATAXIN1 (ATXN1) causes Spinocerebellar ataxia type 1, the functions of wild-type ATXN1 and ATAXIN1-Like (ATXN1L) remain poorly understood. To gain insight into the function of these proteins, we generated and characterized Atxn1L-/- and Atxn1-/- ; Atxn1L-/- double mutant animals. We found that Atxn1L -/- mice have several developmental problems including hydrocephalus, omphalocoele and lung alveolarization defects. These phenotypes are more penetrant and severe in Atxn1-/- ; Atxn1L-/- mice, suggesting that Atxn1 and Atxn1L are functionally redundant.
Publication Title
ATXN1 protein family and CIC regulate extracellular matrix remodeling and lung alveolarization.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We characterized tumor and immune microenvironment (TiME) of malignant pleural mesothelioma (MPM) using immunoproteomic approach to comprehensively understand the landscape to affect prognosis and possibly to predict response to immunotherapy. Time-of-Flight Mass Cytometry (CyTOF) was performed on the tumors of 12 MPM patients. We comprehensively analyzed TiME by developing intuitive models for visualizing single-cell data with statistical inference and performed unsupervised clustering of cell frequency. A clinically relevant protein signature through mass spectrometry and mRNA transcriptome array was tested for its ability to reflect prognosis in three independent cohorts (n=330) and to predict response to immune checkpoint inhibitor therapy in publicly available data and in 10 patients of MPM treated with anti-PD1 therapy. A systematic understanding of antitumor immunity by immunoproteomic characterization of TiME envisions significant progress in developing rational immunotherapeutic strategies in MPM.
Publication Title
Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma.
Sample Metadata Fields
Disease, Disease stage, Treatment
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1s expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer.
Publication Title
ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lung cancer is the leading cause of cancer related death in both men and women in the United States. Recently, Smad4 was discovered to be common somatic alteration in human squamous cell lung cancer. Our goal was to delineate the role of Smad4 in lung cancer. We have shown for the first time that the ablation of Pten and Smad4 in the murine airway epithelium harbors a metastatic proximal adeno-squamous lung cancer.
Publication Title
ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
While most novel tuberculosis (TB) vaccines are designed for delivery via the muscle or skin for enhanced protection in the lung, it has remained poorly understood whether systemic vaccine-induced memory T cells can readily home to the lung mucosa prior to and shortly after pathogen exposure. We have investigated this issue by using a model of parenteral TB immunization and intravascular immunostaining. We find that systemically induced memory T cells are restricted to the blood vessels in the lung, unable to populate either the lung parenchymal tissue or the airway under homeostatic conditions. We further find that after pulmonary TB infection, it still takes many days before such T cells can enter the lung parenchymal tissue and airway. We have identified the acquisition of CXCR3 expression by circulating T cells to be critical for their entry to these lung mucosal compartments. Our findings offer new insights into mucosal T cell biology and have important implications in vaccine strategies against pulmonary TB and other intracellular infections in the lung.
Publication Title
CXCR3 Signaling Is Required for Restricted Homing of Parenteral Tuberculosis Vaccine-Induced T Cells to Both the Lung Parenchyma and Airway.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Facioscapulohumeral muscular dystrophy (FSHD) represents a majorunmet clinical need arising from the progressive weakness and atrophy of skeletal muscles. The dearth of adequate experimental models has severely hampered our understanding of the disease. To date, no treatment is available for FSHD. Human embryonic stem cells (hESCs) potentially represent a renewable source of skeletal muscle cells (SkMCs) and provide an alternative to invasive patient biopsies.Wedeveloped a scalable monolayer system to differentiate hESCs into mature SkMCs within 26 days, without cell sorting or genetic manipulation. Here we show that SkMCs derived from FSHD1-affected hESC lines exclusively express the FSHD pathogenic marker double homeobox 4 and exhibit some of the defects reported in FSHD. FSHD1 myotubes are thinner when compared with unaffected and Becker muscular dystrophy myotubes, and differentially regulate genes involved in cell cycle control, oxidative stress response and cell adhesion. This cellularmodelwill be a powerful tool for studying FSHDandwill ultimately assist in the development of effective treatments for muscular dystrophies.
Publication Title
A Human Pluripotent Stem Cell Model of Facioscapulohumeral Muscular Dystrophy-Affected Skeletal Muscles.
Sample Metadata Fields
Specimen part
View Samples