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GSE88896
Homo sapiens
6 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The role of the transcription factor EB (TFEB) in the control of cellular functions, including in vascular bed, is mostly thought to be the regulation of lysosomal biogenesis and autophagic flux. While this is its best-known function, we report here the ability of TFEB to orchestrate a non-canonical program involved in the control of cell-cycle and VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB deletion halts proliferation by inhibiting the CDK4/Rb pathway, which regulates the cell cycle G1-S transition. In an attempt to overcome this limit, cells compensate by increasing the amount of VEGFR2 on the plasma membrane through a microRNA-mediated mechanism and the control of its membrane trafficking. TFEB transactivates the miR-15a/16-1 cluster, which limits the stability of the VEGFR2 transcript, and negatively modulates the expression of MYO1C, which regulates VEGFR2 delivery to the cell surface. In TFEB knocked-down cells, the reduced and increased amount respectively of miR-15a/16-1 and MYO1C result in the overexpression on plasmamembrane of VEGFR2, which however shows low signaling strength. Using endothelial loss-of-function Tfeb mouse mutants, we present evidence of defects in fetal and newborn mouse vasculature caused by the reduced endothelial proliferation and by the anomalous function of VEGFR2 pathway. Thus, this study revealed a new and unreported function of TFEB that expands its role beyond the regulation of autophagic pathway in the vascular system.
Publication Title
TFEB controls vascular development by regulating the proliferation of endothelial cells.
Sample Metadata Fields
Cell line
View Samples- 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
Efficient endoderm induction from human pluripotent stem cells by logically directing signals controlling lineage bifurcations.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The definitive endoderm germ layer is the provenance of multiple internal organs, including the lungs, liver, pancreas and intestines. Molecular events driving initial endoderm germ layer specification and subsequent anterior-posterior patterning of endoderm into distinct organ primordia remain largely cryptic.
Publication Title
Efficient endoderm induction from human pluripotent stem cells by logically directing signals controlling lineage bifurcations.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human cytomegalovirus (HCMV) induces pro-inflammatory monocytes following infection and we have evidence that EGFR is a key mediator in this early activation. To begin to address how this signalling pathway is responsible for the rapid activation of infected monocytes, we examined the role this pathway played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of genes, including inflammatory genes, were regulated in a EGFR-dependent manner, identifying this pathway as a key cellular control point in the conversion of monocytes to an activated pro-inflammatory state following HCMV infection.
Publication Title
Activation of EGFR on monocytes is required for human cytomegalovirus entry and mediates cellular motility.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus, Homo sapiens, Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Angiotensin II (Ang-II) regulates adrenal steroid production and gene transcription through several signaling pathways. Changes in gene transcription occur within minutes after Ang-II stimulation, causing an acute increase in aldosterone production and subsequent increase in the overall capacity to produce aldosterone. Our goal was to compare the Ang-II regulation of early gene expression and confirm the upregulation of selected genes using quantitative real-time RT-PCR (qPCR) across three species: human, bovine, and rat.
Publication Title
Angiotensin-II acute regulation of rapid response genes in human, bovine, and rat adrenocortical cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human cytomegalovirus (HCMV) induces pro-inflammatory monocytes following infection and we have evidence that phosphatidylinositol 3-kinase [PI(3)K] is a key mediator in this activation. To begin to address how this signalling pathway is responsible for the functional changes in infected monocytes, we examined the role this pathway played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of genes were regulated in a PI(3)K-dependent manner, identifying this pathway as a key cellular control point in the conversion of monocytes to an activated pro-inflammatory state following HCMV infection.
Publication Title
PI3K-dependent upregulation of Mcl-1 by human cytomegalovirus is mediated by epidermal growth factor receptor and inhibits apoptosis in short-lived monocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 239 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Phosphate is essential for healthy bone growth and plays an essential role in fracture repair. Although phosphate deficiency has been shown to impair fracture healing, the mechanisms involved in impaired healing are unknown. More recently, studies have shown that the effect of phosphate deficiency on the repair process varied based on the genetic strain of mice, which is not characterized.
Publication Title
Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MED1 (Mediator complex subunit 1) is expressed by human epidermal keratinocytes and functions as a coactivator of several transcription factors. To elucidate the role of MED1 in keratinocytes, we established keratinocyte-specific MED1-null (MED1epi-/-) mice using the K5Cre-LoxP system.
Publication Title
Roles of MED1 in quiescence of hair follicle stem cells and maintenance of normal hair cycling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 74 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The success of TNF inhibitors for treatment of psoriasis and other inflammatory diseases was previously attributed to blockade of innate immunity. In a clinical trial using etanercept TNF blocking agent to treat psoriasis vulgaris, we used affymetrix gene arrays to analyze broad gene profiles in lesional skin at multiple timepoints during drug treatment (baseline, and weeks 1, 2, 4 and 12) compared to non-lesional skin. This analysis created a temporal model of TNF-dependent gene regulation that informs molecular mechanisms of TNF-mediated inflammation. We identified four gene clusters that were differentially down-modulated during etanercept treatment: the cluster down-regulated most rapidly contained mostly dendritic cell activation genes. Culturing human keratinocytes with TNF, IFNg and IL-17 generated a list of keratinocyte genes regulated by each cytokine. The IL-17 pathway genes were strongly down-modulated early, whereas IFNg pathway genes were not down-modulated until final disease resolution at week 12. Finally, we show that TNF blockade rapidly inhibits IL-12/IL-23 p40 subunit expression, and that p40 neutralization inhibits psoriatic dermal migr-mediated Th17 polarization. We hypothesize that etanercept inhibits myeloid dendritic cell production of IL-23, a Th17 survival cytokine, resulting in rapid downregulation of IL-17 pathway genes. This data links effects of TNF blockade on the innate immune system with the adaptive immune system.
Publication Title
Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MHC-I overexpression in muscle biopsies is a hallmark of inflammatory myopathies.However the mechanisms of MHC-I overexpression in each disease is not well understood. Microarray analysis from MHC-I-microdissected myofibers showed a differential expression signature in each inflammatory myopathy. Innate immunity and IFN-I pathways are upregulated vs healthy controls, specifically in dermatomyositis (DM).
Publication Title
Altered RIG-I/DDX58-mediated innate immunity in dermatomyositis.
Sample Metadata Fields
Specimen part, Disease
View Samples