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GSE90450
Mus musculus
20 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Tristetraprolin (TTP, encoded by Zfp36) regulates the mRNA stability of several important cytokines. Due to the critical role of this RNA-binding protein in the control of inflammation, TTP deficiency leads to the spontaneous development of a complex inflammatory syndrome. So far, this phenotype has been largely attributed to dysregulated production of TNF and IL-23 by myeloid cells such as macrophages or dendritic cells. Here, we generated mice with conditional deletion of TTP in keratinocytes. These mice developed exacerbated inflammation in the imiquimod-induced psoriasis model. Furthermore, these mice progressively developed a spontaneous pathology with systemic inflammation, psoriatic-like skin lesions and dactylitis. Finally, we provide evidence that keratinocyte-derived TNF productin drives the different pathological features. In summary, these findings expand current views on the initiation of psoriasis and related arthritis by revealing the keratinocyte-intrinsic role of TTP.
Publication Title
Tristetraprolin expression by keratinocytes controls local and systemic inflammation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
NextSeq 500
Description
The mammary gland is a highly dynamic organ that mainly develops during puberty. Based on morphology and proliferation analysis, mammary stem cells (MaSCs) are thought to be close to or reside in the terminal end buds (TEBs) during pubertal development. However, exclusive stem cell markers are lacking, and therefore the true identity of MaSCs, including their location, multiplicity, dynamics and fate during branching morphogenesis, has yet to be defined. To gain more insights into the molecular identity and heterogeneity of the MaSC pool, we performed single cell transcriptome sequencing of mammary epithelial cells micro-dissected from ducts and TEBs during puberty. These data show that the behaviour of MaSCs cannot be directly linked to a single expression profile. Instead, morphogenesis of the mammary epithelium relies upon a heterogeneous population of MaSCs that functions long-term as a single equipotent pool of stem cells. Overall design: Ducts and terminal end buds were micro-dissected from the 4th and the 5th murine mammary gland at 5 weeks-of-age, dissociated into single cells, and FACS sorted. Single-cell transcriptomics was performed on live cells using an automated version of CEL-seq2 on live, FACS sorted cells. The StemID algorithm was used to identify clusters of cells corresponding to basal and luminal cells types derived from ducts and terminal end buds.
Publication Title
Identity and dynamics of mammary stem cells during branching morphogenesis.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset progressive muscle disorder caused by a poly-alanine expansion mutation in PABPN1. The hallmark of OPMD is the accumulation of the mutant protein in insoluble nuclear inclusions. The molecular mechanisms associated with disease onset and progression are unknown. We performed a high-throughput cross-species transcriptome study of affected muscles from two OPMD animal models and from patients at pre-symptomatic and symptomatic stages. The most consistently and significantly OPMD-deregulated pathway across species is the ubiquitin-proteasome system (UPS). By analyzing expression profiles, we found that the majority of OPMD-deregulated genes are age-associated. Based on expression trends, disease onset can be separated from progression; the expression profiles of the proteasome-encoding genes are associated with onset but not with progression. In a muscle cell model, proteasome inhibition and the stimulation of immunoproteasome specifically affect the accumulation and aggregation of mutant PABPN1. We suggest that proteasome down-regulation during muscle aging triggers the accumulation of expPABPN1 that in turn enhances proteasome deregulation and leads to intranuclear inclusions (INI) formation.
Publication Title
Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Homo sapiens
- 16 Downloadable Samples
- NextSeq 500
Description
Human dendritic cells were exposed to LPS, in the absence and presence of adenosine receptor 3 inhibitor Overall design: 4 donors, 4 experimental conditions. VUF concentration used was 5 µM, LPS was 500 ng/ml. Exposure times were 6 hours
Publication Title
TLR-Induced IL-12 and CCL2 Production by Myeloid Cells Is Dependent on Adenosine A<sub>3</sub> Receptor-Mediated Signaling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function. We have developed 4C technology, or 3C-on-chip, which allows for an unbiased genome-wide search for DNA loci that contact a given locus in the nuclear space. We demonstrate here that active and inactive genes are engaged in many long-range intrachromosomal interactions and can also form interchromosomal contacts. The active b-globin locus in fetal liver contacts mostly transcribed, but not necessarily tissue-specific, loci elsewhere on chromosome 7, while the inactive locus in fetal brain contacts different, transcriptionally silent, loci. A housekeeping gene in a gene dense region on chromosome 8 forms long-range contacts predominantly with other active gene clusters, both in cis and in trans, and many of these intra- and interchromosomal interactions are conserved between the tissues analyzed. Our data demonstrate that chromosomes fold into areas of active chromatin and areas of inactive chromatin and establish 4C technology as a powerful tool to study nuclear architecture.
Publication Title
Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C).
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression profiling reveals aryl hydrocarbon receptor as a possible target for photobiomodulation when using blue light.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mammalian genomes contain numerous DNA elements with potential transcription regulatory function but unknown target genes. We used transgenic, gain-of-function mice with an ectopic copy of the beta-globin locus control region (LCR) to better understand how regulatory elements dynamically search the genome for target genes. We find that the LCR samples a restricted nuclear sub-volume in which it forms preferential contacts with genes controlled by shared transcription factors. One contacted gene, betah1, located on another chromosome, is upregulated, providing genetic demonstration that mammalian enhancers can function between chromosomes. Upregulation is not pan-cellular but confined to selected jackpot cells significantly enriched for inter-chromosomal LCR-betah1 interactions. This implies that long-range DNA contacts are relatively stable and cell-specific and, when functional, cause variegated expression. We refer to this as spatial effect variegation (SEV). The data provide a dynamic and mechanistic framework for enhancer action, important for assigning function to the one- and three-dimensional structure of DNA.
Publication Title
Variegated gene expression caused by cell-specific long-range DNA interactions.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Photobiomodulation (PBM) with blue light induces a biphasic dose response curve in proliferation of immortalized human keratinocytes (HaCaT), with a maximum anti-proliferative effect reached with 30min (41.4J/cm). The aim of this study was to test the photobiomodulatory effect of 41.4J/cm2 blue light irradiation on ROS production, apoptosis and gene expression at different time points after irradiation of HaCaT cells in vitro. ROS concentration was increased 30min after irradiation. However, already 1h after irradiation, cells were able to reduce ROS and balance the concentration to a normal level. The sudden increase in ROS did not damage the cells, which was demonstrated with FACS analysis where HaCaT cells did not show any sign of apoptosis after blue light irradiation. Furthermore, a time course could be seen in gene expression analysis after blue light, with an early response of stimulated genes already 1h after blue light irradiation, leading to the discovery of the aryl hydrocarbon receptor as possible target for blue light irradiation.
Publication Title
Gene expression profiling reveals aryl hydrocarbon receptor as a possible target for photobiomodulation when using blue light.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Photobiomodulation (PBM) with blue light induces a biphasic dose response curve in proliferation of immortalized human keratinocytes (HaCaT), with a maximum anti-proliferative effect reached with 30min (41.4J/cm). The aim of this study was to test the photobiomodulatory effect of 41.4J/cm2 blue light irradiation on ROS production, apoptosis and gene expression at different time points after irradiation of HaCaT cells in vitro. ROS concentration was increased 30min after irradiation. However, already 1h after irradiation, cells were able to reduce ROS and balance the concentration to a normal level. The sudden increase in ROS did not damage the cells, which was demonstrated with FACS analysis where HaCaT cells did not show any sign of apoptosis after blue light irradiation. Furthermore, a time course could be seen in gene expression analysis after blue light, with an early response of stimulated genes already 1h after blue light irradiation, leading to the discovery of the aryl hydrocarbon receptor as possible target for blue light irradiation.
Publication Title
Gene expression profiling reveals aryl hydrocarbon receptor as a possible target for photobiomodulation when using blue light.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Photobiomodulation (PBM) with blue light induces a biphasic dose response curve in proliferation of immortalized human keratinocytes (HaCaT), with a maximum anti-proliferative effect reached with 30min (41.4J/cm). The aim of this study was to test the photobiomodulatory effect of 41.4J/cm2 blue light irradiation on ROS production, apoptosis and gene expression at different time points after irradiation of HaCaT cells in vitro. ROS concentration was increased 30min after irradiation. However, already 1h after irradiation, cells were able to reduce ROS and balance the concentration to a normal level. The sudden increase in ROS did not damage the cells, which was demonstrated with FACS analysis where HaCaT cells did not show any sign of apoptosis after blue light irradiation. Furthermore, a time course could be seen in gene expression analysis after blue light, with an early response of stimulated genes already 1h after blue light irradiation, leading to the discovery of the aryl hydrocarbon receptor as possible target for blue light irradiation.
Publication Title
Gene expression profiling reveals aryl hydrocarbon receptor as a possible target for photobiomodulation when using blue light.
Sample Metadata Fields
No sample metadata fields
View Samples