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GSE10740
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Na+/H+ exchanger 3 (NHE3) provides a major route for intestinal Na+ absorption. It has been considered as a target of proinflammatory cytokines and enteropathogenic bacteria and impaired NHE3 expression and/or activity may be responsible for inflammation-associated diarrhea.
Publication Title
Colonic gene expression profile in NHE3-deficient mice: evidence for spontaneous distal colitis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
There is a good deal of indirect evidence that improved insulin sensitivity may contribute to improved lifespan of mice in which aging has been slowed by mutations, drugs, or dietary means, even in stocks of mice that do not show signs of late-life diabetes. Peripheral responses to insulin can be augmented by over-expression of Syntaxin 4 (Syn4), a membrane SNARE protein. We show here that Syn4 transgenic (Tg) mice live approximately 33% longer than controls, and show increased peripheral insulin sensitivity, even at ages where controls show age-related insulin resistance. Hence, presumably Syn4 Tg mice spend more hours of each day under normoglycemic conditions, which may slow multiple aspects of aging and thereby extend lifespan, even in non-diabetic mice.
Publication Title
Syntaxin 4 Overexpression Ameliorates Effects of Aging and High-Fat Diet on Glucose Control and Extends Lifespan.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
DNA methylation plays a vital role in the cell, but loss-of-function mutations of the maintenance methyltransferase DNMT1 in normal human cells are lethal, precluding target identification, and existing hypomorphic lines are tumour cells. We generated instead a hypomorphic series in normal hTERT-immortalised fibroblasts using stably integrated short hairpin RNA. Approx 2/3 of sites showed demethylation as expected, with 1/3 showing hypermethylation, and targets were shared between the three independently-derived lines. Enrichment analysis indicated significant losses at promoters and gene bodies with four gene classes most affected: 1)protocadherins, which are key to neural cell identity; 2)genes involved in fat homeostasis/body mass determination; 3)olfactory receptors and 4) cancer/testis antigen (CTA) genes. Overall effects on transcription were relatively small in these fibroblasts, but CTA genes showed robust derepression. Comparison with siRNA-treated cells indicated that shRNA lines show substantial remethylation over time. Regions showing persistent hypomethylation in the shRNA lines were associated with polycomb repression, and were derepressed on addition of an EZH2 inhibitor. Persistent hypermethylation in shRNA lines was in contrast associated with poised promoters. Our results suggest polycomb marking blocks remethylation and indicate the sensitivity of key neural, adipose, and cancer-associated genes to chronic depletion of maintenance methylation activity.
Publication Title
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Synovial biopsies were obtained from osteoarthritis (OA) synovium to find genes upregulated during OA.
Publication Title
Functional Tissue Analysis Reveals Successful Cryopreservation of Human Osteoarthritic Synovium.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation.
Sample Metadata Fields
Sex, Cell line, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V3.0 expression beadchip
Description
The expansion of repressive epigenetic marks has been implicated in heterochromatin formation during embryonic development, but the general applicability of this mechanism is unclear. Here we show that nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into non-overlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. However, the global landscape of these repressive marks remains unchanged upon SAHF formation, suggesting that in somatic cells heterochromatin can be formed through the spatial repositioning of pre-existing repressively marked histones. This model is reinforced by the correlation of pre-senescent replication timing with both the subsequent layered structure of SAHFs and the global landscape of the repressive marks, allowing us to integrate microscopic and genomic information. Furthermore, modulation of SAHF structure does not affect the occupancy of these repressive marks nor vice versa. These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events.
Publication Title
Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation.
Sample Metadata Fields
Sex, Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Stem cells, with their potential to generate different lineages, could offer a solution by replacing damaged or lost cells within the inner ear. We have shown that human embryonic stem cells can be induced to differentiate into otic progenitors, and then into hair cell-like cells and neurons that display expected electrophysiological properties. More importantly, once these otic progenitors are transplanted into animals with induced hearing loss, they differentiate and elicit a significant recovery of auditory function. The generation of otic progenitors is triggered by FGF signalling. In this dataset we have analysed the global gene expression profile of undifferentiated hESCs and compared with cultures that have been treated with FGF3 and 10, the two ligands involved in otic induction, or cultures that have been allowed to differentiate under basal conditions without FGF (DFNB).
Publication Title
Restoration of auditory evoked responses by human ES-cell-derived otic progenitors.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of genes that are differentially regulated in fibroblasts derived from dysplastic oral mucosa and oral squamous cell carcinoma compared to fibroblasts derived from normal oral mucosa.
Publication Title
Identification of two distinct carcinoma-associated fibroblast subtypes with differential tumor-promoting abilities in oral squamous cell carcinoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression array analysis component. Ligand-dependent transcription by the nuclear receptor glucocorticoid receptor (GR) is mediated by interactions with co-regulators. The role of these interactions in determining selective binding of GR to regulatory elements remains unclear. Recent findings indicate a large fraction of genomic GR binding coincides with chromatin that is accessible prior to hormone treatment, suggesting that receptor binding is dictated by proteins that maintain chromatin in an open state. Combining nucleolytic cleavage and chromatin immunoprecipitation with high-throughput sequencing, we identify the activator protein 1 (AP1) as a major partner for productive GR-chromatin interactions. AP1 is critical for GR-regulated transcription and recruitment to co-occupied regulatory elements, illustrating an extensive AP1-GR interaction network. Importantly, the maintenance of baseline chromatin accessibility facilitates GR recruitment and is dependent on AP1 binding. We propose a model where the basal occupancy of transcription factors act to prime chromatin and direct inducible transcription factors to select regions in the genome.
Publication Title
Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding.
Sample Metadata Fields
Sex, Cell line, Treatment, Time
View Samples