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GSE144397
Homo sapiens
96 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here, we examined the possibility that the epigenetic state of enhancers determines senescent cell fate. We explored this by generating time-resolved transcriptomes and epigenome profiles during oncogenic RAS-induced senescence and validating central findings in different cell biology and disease models of senescence. Through integrative analysis and functional validation, we reveal links between enhancer chromatin, transcription factor recruitment and senescence competence. We demonstrate that activator protein 1 (AP-1) ‘pioneers’ the senescence enhancer landscape and defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells. Together, our findings enabled us to manipulate the senescence phenotype with potential therapeutic implications.
Publication Title
AP-1 imprints a reversible transcriptional programme of senescent cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Clinical symptoms of dengue virus (DENV) infection, the most prevalent arthropod-borne viral disease, range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on an individuals health. We used an integrated approach of transcriptional profiling and immunological analysis to compare a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune response pathways were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T and B cell activation pathways were differentially regulated, independent of viral load and previous DENV infection history. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals, as demonstrated by increased activation of T cell apoptosis-related pathways and FcRIIB signaling associated with decreased anti-DENV specific antibody concentrations. Taken together, our data illustrate that symptom-free DENV infection in children is associated with determined by increased activation of the adaptive immune compartment and proper control mechanisms, leading to elimination of viral infection without excessive immune activation, with implications for novel vaccine development strategies
Publication Title
Increased adaptive immune responses and proper feedback regulation protect against clinical dengue.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sumoylation coordinates the repression of inflammatory and anti-viral gene-expression programs during innate sensing.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 19 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here, we examined the possibility that the epigenetic state of enhancers determines senescent cell fate. We explored this by generating time-resolved transcriptomes and epigenome profiles during oncogenic RAS-induced senescence and validating central findings in different cell biology and disease models of senescence. Through integrative analysis and functional validation, we reveal links between enhancer chromatin, transcription factor recruitment and senescence competence. We demonstrate that activator protein 1 (AP-1) 'pioneers' the senescence enhancer landscape and defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells. Together, our findings enabled us to manipulate the senescence phenotype with potential therapeutic implications.
Publication Title
AP-1 imprints a reversible transcriptional programme of senescent cells.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Hepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/�-catenin signaling. Microarray analysis identified two tumor subclasses resembling distinct phases of liver development, and a 16-gene signature discriminated invasive and metastatic hepatoblastomas, and predicted prognosis with high accuracy. <br></br>
Publication Title
Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Necroptosis microenvironment directs lineage commitment in liver cancer.
Sample Metadata Fields
Sex, Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Bone marrow derived dendritic cells were generated from Ubc9[fl;-] and Ubc9[+/+] mice. After in vitro derivation in the presence of GM-CSF, dendritic cells were treated with tamoxifen for four days to cause CreERT2 activation, and induce Ubc9 floxed allele deletion. This allowed comparative transcriptomic analysis of Ubc9[+/+] and Ubc9[-/-] dendritic cells unstimulated or stimulated with 10ng/ml LPS for one hour and six hours.
Publication Title
Sumoylation coordinates the repression of inflammatory and anti-viral gene-expression programs during innate sensing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The satellite cell of skeletal muscle provides a paradigm for quiescent and activated tissue stem cell states. We have carried out transcriptome analyses by comparing satellite cells from adult skeletal muscles, where they are mainly quiescent, with cells from growing muscles, regenerating (mdx) muscles, or with cells in culture, where they are activated. Our study gives new insights into the satellite cell biology during activation and in respect with its niche.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples