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GSE65366
Homo sapiens
28 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The mechanisms by which the epidermis responds to disturbances in barrier function and restores homeostasis are unknown. With a disruption of the epidermal barrier, water is lost resulting in an increase in extracellular sodium concentration. We demonstrate that the sodium channel Nax functions as the sodium sensor. With increased extracellular sodium, Nax up-regulates prostasin which results in activation of the sodium channel ENaC, resulting in increased sodium flux and increased downstream mRNA synthesis of inflammatory mediators. The same pathways are present in lung epithelial cells.
Publication Title
Sodium channel Nax is a regulator in epithelial sodium homeostasis.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways which persists for at least 12 weeks. CRS is one of the most common chronic diseases in adults in the United States, affecting over 30 million Americans. CRS is frequently divided into 2 types: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Histologic studies have demonstrated significant tissue eosinophilia in CRSwNP. T cells in the mucosa are elevated in both forms of CRS and are skewed towards Th2 cytokine expression in CRSwNP. However pathogenic role of CRS has not been fully explored. To screen for pathogenic factors in CRS, we performed a microarray study. We collected uncinate tissues (UT) from 6 subjects with CRSsNP, 6 subjects with CRSwNP and 6 control subjects and nasal polyp (NP) tissues from 6 subjects with CRSwNP and then evaluated gene expression profiles using Affymetrix Human Genome U133 plus 2.0 array.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus, Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CD95 (also called FAS and APO-1) is a prototypical death receptor that
Publication Title
CD95 promotes tumour growth.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The neuroectoderm is patterned along a rostral-caudal axis in response to localized factors in the embryo, but exactly how these factors act as positional information for this patterning is not yet fully understood. Here, using the self-organizing properties of mouse embryonic stem cell (ESC), we report that ESC-derived neuroectoderm self-generates a Six3+ rostral and a Irx3+ caudal bipolarized patterning. In this instance, localized Fgf signaling performs dual roles, as it regulates Six3+ rostral polarization at an earlier stage and promotes Wnt signaling at a later stage. The Wnt signaling components are differentially expressed in the polarized tissues, leading to genome-wide Irx3+ caudal-polarization signals. Surprisingly, differentially expressed Wnt agonists and antagonists have essential roles in orchestrating the formation of a balanced rostral-caudal neuroectoderm pattern. Together, our findings provide key processes for dynamic self-patterning and evidence that a temporally and locally regulated interaction between Fgf and Wnt signaling controls self-patterning in ESC-derived neuroectoderm.
Publication Title
Self-patterning of rostral-caudal neuroectoderm requires dual role of Fgf signaling for localized Wnt antagonism.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The epiblast (foremost embryonic ectoderm) generates all three germ layers and therefore has crucial roles in the formation of all mammalian body cells. Regulation of epiblast gene expression is poorly understood due to the difficulty of manipulating epiblast tissues in vivo. In the present study, using the self-organizing properties of embryonic stem cells (ESCs), we generated and characterized epiblast-like tissue in three-dimensional (3D) culture. We identified significant genome-wide expression changes in this epiblast-like tissue. Additionally, we identified the significance of the Fgf/Erk and ectoderm formation pathways, using the bioinformatics resource IPA and DAVID. We first focused on Fgf5, which ranked in the top 10 among discovered genes. Toward functional analysis of Fgf5, we developed efficient methods of genome engineering (CRISPR/Cas9) and RNA interference (RNAi). Notably, we show one-step generation of an Fgf5 reporter line, null and in/del mutants. Furthermore, mutation types correlated well with CRISPR/Cas9 activity. For time- and dose-dependent depletion of Fgf5 over the course of development, we generated an ESC line harboring a drug-inducible short hairpin RNA cassette integrated by the Tol2 transposon system (pRNAi). Our methods provide a framework for a broad array of applications in the areas of mammalian genetics and molecular biology to understand development and to improve future therapeutics.
Publication Title
Establishment of Functional Genomics Pipeline in Mouse Epiblast-Like Tissue by Combining Transcriptomic Analysis and Gene Knockdown/Knockin/Knockout, Using RNA Interference and CRISPR/Cas9.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To characterize underlying changes in the retinal pigment epithelium (RPE)/choroid with age, we produced gene expression profiles for the RPE/choroid and compared the transcriptional profiles of the RPE/choroid from young and old mice. The changes in the aged RPE/choroid suggest that the tissue has become immunologically active. Such phenotypic changes in the normal aged RPE/choroid may provide a background for the development of age-related macular degeneration.
Publication Title
The aged retinal pigment epithelium/choroid: a potential substratum for the pathogenesis of age-related macular degeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
PRC, a member of the PGC-1 coactivator family, is responsive to serum growth factors and up regulated in proliferating cells. Here, we investigated its in vivo role by stably silencing PRC expression with two different short hairpin RNAs (shRNA#1 and shRNA#4) that were lentivirally introduced into U2OS cells. ShRNA#1 transductants exhibited nearly complete knockdown of PRC protein whereas shRNA#4 transductants expressed PRC protein at approximately 15 percent of the control level. Complete PRC silencing by shRNA#1 resulted in a severe inhibition of respiratory growth, reduced expression of respiratory protein subunits from complexes I, II, III and IV, markedly lower complex I and IV respiratory enzyme levels and diminished mitochondrial ATP production. Surprisingly, shRNA#1 transductants exhibited a striking proliferation of abnormal mitochondria that were devoid of organized cristae and displayed severe membrane abnormalities. Although shRNA#4 transductants had normal respiratory subunit expression and a moderately diminished respiratory growth rate, both transductants showed markedly reduced growth on glucose accompanied by inhibition of G1/S cell cycle progression. Microarray analysis revealed striking overlaps in the genes affected by PRC silencing in the two transductants and the functional identities of these overlapping genes were consistent with the observed mitochondrial and cell growth phenotypes. The consistency between phenotype and PRC expression levels in the two independent transductant lines argues that the defects result from PRC silencing and not from off target effects. These results support a role for PRC in the integration of pathways directing mitochondrial respiratory function and cell growth.
Publication Title
Short hairpin RNA-mediated silencing of PRC (PGC-1-related coactivator) results in a severe respiratory chain deficiency associated with the proliferation of aberrant mitochondria.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray data on H9 hESC-derived cardiomyocytes (d30) treated with 0, 0.1, 1, or 10 uM of doxorubicin for 24 h
Publication Title
Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 380 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sleep and affective behaviors are highly interrelated phenotypes, commonly altered in a variety of neuropsychiatric diseases, including major depressive disorder (MDD). To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J x 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions, including the frontal cortex, hippocampus, thalamus, and hypothalamus. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Utilizing publicly available transcriptomic datasets collected from sleep-deprived mice and major depressive disorder (MDD) patients, we identified three cortical gene networks altered by sleep/wake changes and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity-dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.
Publication Title
Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 224 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Favorable Histology WTs (FHWT) are genetically heterogeneous and the pathogenesis for the majority is not known; therefore, we sought to identify and characterize distinctive subsets within FHWT and to place each subset within their clinical and developmental context.
Publication Title
No associated publication
Sample Metadata Fields
Age
View Samples