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GSE36641
Homo sapiens
10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cellular senescence is a stable proliferation arrest in response to stress, associated with an altered secretory pathway (Senescence Associated Secretory Phenotype (SASP)). Senescence-associated proliferation arrest and the SASP are thought to act in concert to promote tumor suppression and tissue aging. While chromatin regulation and down regulation of lamin B1 have been implicated as effectors of cell senescence, functional interactions between them are poorly understood. We compared the genome-wide distributions of H3K4me3 and H3K27me3 between proliferating and senescent primary human cells and found dramatic differences, including large-scale domains of H3K4me3- and H3K27me3-enriched mesas and H3K27me3-depleted canyons in senescent cells. Senescent mesas form at the sites of lamin B1-associated domains (LADs) in proliferating cells. Mesas also overlap with regions that exhibit DNA hypomethylation in cancer, suggesting that chromatin changes in pre-malignant senescent cells foreshadow epigenetic changes in cancer. Proliferating fibroblasts from Hutchinson-Gilford Progeria Syndrome patients expressing mutant lamin A (progerin) also show evidence of H3K4me3 mesas, suggesting a link between premature chromatin changes and accelerated cell senescence and tissue aging. In contrast, canyons form mostly in between LADs and are enriched in genes, gene promoters and enhancers. Strikingly, H3K27me3 loss in canyons is correlated with upregulation of key senescence genes, including genes comprising the SASP, indicating a link between global changes in chromatin structure and local regulation of gene expression. Finally, premature reduction of lamin B1 in midlife proliferating cells triggers formation of senescence-associated mesas and canyons and accelerated senescence. Together, our data illustrate a profound reorganization of chromatin during senescence, and suggest that down regulation of lamin B1 in senescence is a key trigger of global and local chromatin changes that impact gene expression, aging and cancer.
Publication Title
Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Differential gene expression profiles were observed in response to Hras in either wild-type or Ppar-beta null primary keratinocytes and differentail gene edxpression profiles by GW0742 were only found in wild-type keratinocytes.
Publication Title
Peroxisome proliferator-activated receptor β/δ cross talks with E2F and attenuates mitosis in HRAS-expressing cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The human and mouse aryl hydrocarbon receptor (hAHR and mAHRb) share limited (58%) transactivation domain sequence identity. Compared to the mAHRb allele, the hAHR displays 10-fold lower relative affinity for prototypical ligands such as 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). However, in previous studies we have demonstrated that the hAHR can display a higher relative ligand binding affinity than the mAHRb for specific AHR ligands such as indirubin. Each receptor has also been shown to differentially recruit LXXLL co-activator-motif proteins and to utilize different TAD subdomains in gene transactivation. Using hepatocytes isolated from C57BL6/J mice (Ahrb/b) and AHRTtr transgenic mice which express hAHR protein specifically in hepatocytes, we investigated whether the hAHR and mAHRb differentially regulate genes. Microarray and quantitative-PCR analysis of Ahrb/b and AHRTtr primary-mouse hepatocytes treated with 10 nM TCDD revealed that a number of established AHR target genes such as Cyp1a1 and Cyp1b1 are significantly induced by both receptors. Remarkably, of the 1752 genes induced by mAHRb and 1186 genes induced by hAHR, only 265 genes (<10%) were significantly activated by both receptors in response to TCDD. Conversely of the 1100 and 779 genes significantly repressed in mAHRb and hAHR hepatocytes respectively, only 462 (<25%) genes were significantly repressed by both receptors in response to TCDD treatment. Genes identified as differentially expressed are known to be involved in a number of biological pathways, including cell proliferation and inflammatory response which suggests that compared to the mAHRb, the hAHR may play contrasting roles in TCDD-induced toxicity and endogenous AHR-mediated gene regulation.
Publication Title
Differential gene regulation by the human and mouse aryl hydrocarbon receptor.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
IRE1a is a critical modulator of the unfolded protein response. Its RNAse activity generates the mature transcript for the XBP1 transcription factor and also degrades other ER associated mRNAs in a process termed Regulated IRE1a Dependent mRNA Decay or RIDD. To determine if IRE1a is critical in the response to oncogenic Ras we used ShRNA to knockdown Ire1a or Xbp1 in primary mouse epidermal keratinocytes transduced with a v-HRAS retrovirus.
Publication Title
ER stress and distinct outputs of the IRE1α RNase control proliferation and senescence in response to oncogenic Ras.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The AhR is a ligand activated transcription factor that may be important in normal skin physiology. We compared gene expression profiles between AhR Wt and AhR KO primary mouse keratinocyte cultures. We identified 391 genes that were differentially expressed with a 1.5 fold cutoff and p<.05, and identified the AhR as an important regulator of genes involved in normal epidermal differentiation.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Immune memory cells are poised to rapidly expand and elaborate effector functions upon reinfection. However, despite heightened readiness to respond, memory cells exist in a functionally quiescent state. The paradigm is that memory cells remain inactive due to lack of TCR stimuli. Here we report a unique role of Tregs in orchestrating memory quiescence by inhibiting effector and proliferation programs through CTLA-4. Loss of Tregs resulted in activation of genome-wide transcriptional programs characteristic of potent effectors, and both developing and established memory quickly reverted to a terminally differentiated (KLRG-1hi/IL-7Rlo/GzmBhi) phenotype, with compromised metabolic fitness, longevity, polyfunctionality and protective efficacy. CTLA-4, an inhibitory receptor overexpressed on Tregs, functionally replaced Tregs in trans to rescue Treg-less memory defects and restore homeostasis of secondary mediators as well. These studies present CD28-CTLA-4-CD80/CD86 axis as a novel target to potentially accelerate vaccine-induced immunity and improve T-cell memory quality in current cancer immunotherapies proposing transient Treg-depletion.
Publication Title
Quiescence of Memory CD8(+) T Cells Is Mediated by Regulatory T Cells through Inhibitory Receptor CTLA-4.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Myeloid progenitors derived from antibiotic-treated mice have cell-intrinsic functional defects. In this microarray dataset, the transcriptomes of bone marrow myeloid progenitors from antibiotic-treated and control mice are compared.
Publication Title
Microbiota-dependent signals are required to sustain TLR-mediated immune responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 288 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A circadian gene expression atlas in mammals: implications for biology and medicine.
Sample Metadata Fields
Specimen part
View Samples