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GSE15118
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mice that develop benign cartilage lesions due to overexpression of Gli2 in chondrocytes developed lesions similar to chondrosarcomas when also deficient in p53. Gli2 overexpression and p53 deficiency had opposing effects on chondrocyte differentiation, but had additive effects negatively regulating apoptosis. Regulation of Igfbp3 expression and IGF signaling by Gli and p53 integrated their effect on apoptosis. Treatment of human chondrosarcomas or fetal mouse limbs explants with IGFBP3 or by blocking IGF increased the apoptosis rate, and mice expressing Gli2 developed substantially fewer tumors when also deficient for Igf2. IGF signaling meditated apoptosis regulates the progression to malignant chondrosarcoma.
Publication Title
Gli2 and p53 cooperate to regulate IGFBP-3- mediated chondrocyte apoptosis in the progression from benign to malignant cartilage tumors.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
Microbial functions in the host physiology are a result of co-evolution between microbial communities and their hosts. Here we show that cold exposure leads to marked shift of the microbiota composition, referred to as cold microbiota. Transplantation of the cold microbiota to germ-free mice is sufficient to increase the insulin sensitivity of the host, and enable complete tolerance to cold partly by promoting the white fat browning, leading to increased energy expenditure and fat loss. During prolonged cold however, the body weight loss is attenuated, caused by adaptive mechanisms maximising caloric uptake and increasing intestinal, villi and microvilli lengths. This increased absorptive surface is promoted by the cold microbiota - effect that can be diminished by co-transplanting the most downregulated bacterial strain from the Verrucomicrobia phylum, Akkermansia muciniphila, during the cold microbiota transfer. Our results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand. Overall design: Mice were kept 30 days at room temperature or at 6C, 2 per cage, under SPF conditions, with or without administration of antibiotic coctail in drinking water (whole microbiota depletion). Fasted 5h before sacrifice. Segments of proximal jejunum were isoated, flushed gently with PBS and frozen. Each of 12 samples is a pool of two biological replicates (2 biological replicates of the same condition combined into one sample)
Publication Title
Gut Microbiota Orchestrates Energy Homeostasis during Cold.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
PFAPA, the syndrome of periodic fever associated with aphthous stomatitis, pharyngitis and/or cervical adenitis, is the most common periodic fever disease in children. Cases are mostly sporadic; the etiopathogenesis is unknown.
Publication Title
Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade.
Sample Metadata Fields
Sex, Age, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 220 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Wnt pathway is dysregulated in CLL-We characterized Wnt pathway gene expression in normal B and CLL-B cells and identified Wnt targets in normal B and CLL-B cells through this data set.
Publication Title
Somatic mutation as a mechanism of Wnt/β-catenin pathway activation in CLL.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic non-healing venous leg ulcers (VLUs) are a widespread debilitating disease with high morbidity and associated costs, as approximately $15 billion annually are spent on the care of VLUs. Despite their socioeconomic burden, there is a paucity of novel treatments targeted towards healing VLUs, which can be attributed to both lack of pathophysiologic insight into VLU development as well as lack of knowledge regarding biologic actions of VLU-targeted therapies. Currently, the bioengineered bilayered living cellular construct (BLCC) skin substitute is the only FDA-approved biologic treatment for healing VLUs. To elucidate the mechanisms through which the BLCC promotes healing of chronic VLUs, we conducted a clinical trial (NCT01327937) in which patients with non-healing VLUs were treated with either standard care (compression therapy) or with BLCC together with standard care. Tissue was collected from the VLU edge before and 1 week after treatment, and samples underwent comprehensive microarray, mRNA and protein analyses. Ulcers treated with BLCC skin substitute displayed three distinct patterns suggesting the mechanisms by which BLCC shifted a non-healing into a healing tissue response: it modulated inflammatory and growth factor signaling; it activated keratinocytes; and it attenuated Wnt/-catenin signaling. In these ways, BLCC application orchestrated a shift of the chronic non-healing ulcer microenvironment into a distinctive healing milieu resembling that of an acute, healing wound. Our findings also provide first patient-derived in vivo evidence of specific biologic processes that can be targeted in the design of therapies to promote healing of chronic VLUs.
Publication Title
A bioengineered living cell construct activates an acute wound healing response in venous leg ulcers.
Sample Metadata Fields
Specimen part, Disease stage, Time
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
As part of a large genetic evolution study we also acquired 3'UTR expression arrays at two time points for the same 18 patients with CLL.
Publication Title
Evolution and impact of subclonal mutations in chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Klotho is critical for the survival of triple negative breast cancer (TNBC) cells HCC1395, since its depletion leads to decreased cell viability, cell cycle arrest and apoptosis.
Publication Title
γKlotho is a novel marker and cell survival factor in a subset of triple negative breast cancers.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Diabetic foot ulcers (DFUs) are the leading cause of lower leg amputations in diabetic population. To better understand molecular pathophysiology of DFUs we used patients specimens and genomic profiling. We identified 3900 genes specifically regulated in DFUs. Moreover, we compared DFU to human skin acute wound (AW) profiles and found DNA repair mechanisms and regulation of gene expression among the processes specifically suppressed in DFUs, whereas essential wound healing-related processes, inflammatory/immune response or cell migration, were not activated properly. To identify potential regulators of DFU-specific genes, we used upstream target analysis. We found miR-15/16 family enriched in DFUs, but not in AW, which was confirmed by qPCR. We found that infection with the most common DFU colonizer, Staphylococcus aureus, triggers induction of miR-15-5p, which in turn, targets multiple DFU-specific genes, including genes involved in DNA repair (WEE1, MSH2 and RAD50) and the regulator of inflammatory pathway, IKBKB. Induction of miR-15b-5p, either by miR-mimic transfection in vitro or by S. aureus infection of acute wounds ex vivo, suppressed both WEE1 and IKBKB. Consequently, we detected an increase in DNA double strand breaks in DFUs. In summary, our data indicate that S. aureus infection, via induction of miR-15b-5p, may lead to suppression of DNA repair mechanisms and a sub-optimal inflammatory response, contributing to pathophysiology of DFU patients
Publication Title
Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Targets of Retinoic Acid (RA) were identified in primary human epidermal keratinocytes grown in the presence or absence of all-trans retinoic acid for 1, 4, 24, 48 and 72 hours. Targets of Thyroid Hormone (T3) were identified in primary human epidermal keratinocytes grown in the presence or absence of the hormone; same controls as for RA.
Publication Title
Retinoid-responsive transcriptional changes in epidermal keratinocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With an extremely poor five-year survival rate of only 15%, identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutation spectra from the whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a novel mutational signature in EACs defined by a high prevalence of A to C transversions at Ap*A dinucleotides. Statistical analysis of the exome data identified 26 genes that are mutated at a significant frequency. Of these 26 genes, only four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include several chromatin modifying factors and candidate contributors to EAC: SPG20, TLR4, ELMO1, and DOCK2. Notably, functional analyses of EAC-derived mutations in ELMO1 increase cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis.
Publication Title
Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage, Race
View Samples