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Drosophila melanogaster
21 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Mitochondria are able to modulate cell state and fate during normal and pathophysiologic conditions through a nuclear mediated mechanism collectively termed as a retrograde response. Our previous studies in Drosophila have clearly established that progress through the cell cycle is precisely regulated by the intrinsic activity of the mitochondrion by specific signaling cascades mounted by the cell. As a means to further our understanding of how mitochondrial energy status affects nuclear control of basic cell decisions we have employed Affymetrix microarray-based transcriptional profiling of Drosophila S2 cells knocked down for the gene encoding subunit Va of the complex IV of the mitochondrial electron transport chain. The profiling data identifies up-regulation of glycolytic genes and metabolic studies confirm this increase in glycolysis. The transcriptional portrait which emerges implicates many signaling systems, including a p53 response, an insulin response, and up-regulation of conserved mitochondrial responses. This rich dataset provides many novel targets for further understanding the mechanism whereby the mitochondrion may direct cellular fate decisions. The data also provides a salient model of the shift of metabolism from a predominately oxidative state towards a predominately aerobic glycolytic state, and therefore provides a model of energy substrate management not unlike that found in cancer.
Publication Title
Expression profiling of attenuated mitochondrial function identifies retrograde signals in Drosophila.
Sample Metadata Fields
Cell line
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GSE4412- Homo sapiens
- 169 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Diffuse infiltrating gliomas are the most common primary brain malignancy found in adults, and Glioblastoma multiforme, the highest grade glioma, is associated with a median survival of 7 months. Transcriptional profiling has been applied to 85 gliomas from 74 patients to elucidate glioma biology, prognosticate survival, and define tumor sub-classes. These studies reveal that transcriptional profiling of gliomas is more accurate at predicting survival than traditional pathologic grading, and that gliomas characteristically express coordinately regulated genes of one of four molecular signatures: neurogenesis, synaptic transmission, mitotic, or extra-cellular matrix. Elucidation of these survival associated molecular signatures will aid in tumor prognostication and define targets for future directed therapy.
Publication Title
Gene expression profiling of gliomas strongly predicts survival.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Homo sapiens
- 167 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Migrated from 1.6 id: 1015897590491013 GEDP id: 760 In current clinical practice, histology-based grading of diffuse infiltrative gliomas is the best predictor of patient survival time. Yet histology provides little insight into the underlying biology of gliomas and is limited in its ability to identify and guide new molecularly targeted therapies. We have performed large-scale gene expression analysis using the Affymetrix HG U133 oligonucleotide arrays on 85 diffuse infiltrating gliomas of all histologic types to assess whether a gene expression-based, histology-independent classifier is predictive of survival and to determine whether gene expression signatures provide insight into the biology of gliomas. We found that gene expression-based grouping of tumors is a more powerful survival predictor than histologic grade or age. The poor prognosis samples could be grouped into three different poor prognosis groups, each with distinct molecular signatures. We further describe a list of 44 genes whose expression patterns reliably classify gliomas into previously unrecognized biological and prognostic groups: these genes are outstanding candidates for use in histology-independent classification of high-grade gliomas. The ability of the large scale and 44 gene set expression signatures to group tumors into strong survival groups was validated with an additional external and independent data set from another institution composed of 50 additional gliomas. This demonstrates that large-scale gene expression analysis and subset analysis of gliomas reveals unrecognized heterogeneity of tumors and is efficient at selecting prognosis-related gene expression differences which are able to be applied across institutions.
Publication Title
Gene expression profiling of gliomas strongly predicts survival.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Human Gene 2.0 ST Array (hugene20st), Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
NF-κB activation impairs somatic cell reprogramming in ageing.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Transcriptional profiling of human control and Nstor-Guillermo Progeria Syndrome (NGPS) mesenchymal stem cells (MSCs).
Publication Title
NF-κB activation impairs somatic cell reprogramming in ageing.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Dietary intervention constitutes a feasible approach for modulating metabolism and improving healthspan and lifespan. Methionine restriction (MR) delays the appearance of age-related diseases and increases longevity in normal mice. However, the effect of MR on premature aging remains to be elucidated. Here, we describe that MR extends lifespan in two different mouse models of Hutchinson-Gilford progeria syndrome (HGPS) by reversing the transcriptome alterations in inflammation and DNA-damage response genes present in this condition. Further, MR improves the lipid profile and alters the levels of bile acids, both in wild-type and in progeroid mice. Notably, treatment with the bile acid cholic acid improves healthspan and lifespan in vivo. These results suggest the existence of a metabolic pathway involved in the longevity extension achieved by MR and support the possibility of dietary interventions for treating progeria.
Publication Title
Methionine Restriction Extends Lifespan in Progeroid Mice and Alters Lipid and Bile Acid Metabolism.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase paralleling the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b-/- mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. Atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohns disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b-/- mice. Taken together, these results provide additional evidence on the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that Atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency
Publication Title
ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Defining the aging-cancer relationship is a challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate many features of aging. However, their short lifespan and cell-intrinsic and -extrinsic alterations restrict the application and interpretation of carcinogenesis protocols. To circumvent these limitations we have generated Zmpste24 mosaic mice. Interestingly, these mice develop normally - revealing cell-extrinsic mechanisms are preeminent in progeria- and display decreased incidence of infiltrating oral carcinomas. Moreover, ZMPSTE24 knock-down reduces human cancer cell invasiveness. Our results disclose the ZMPSTE24-prelamin A system as an example of antagonistic pleiotropy on cancer and aging, support the potential of cell-based and systemic therapies for progeria, and highlight ZMPSTE24 as a new anticancer target.
Publication Title
Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Transcriptional profiling of human acute myeloid leukemia cells lines HEL and SET2 transduced with an IGF1R shRNA and miR-125a sponge.
Publication Title
Loss of the proteostasis factor AIRAPL causes myeloid transformation by deregulating IGF-1 signaling.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent development of the first therapeutic approaches for this disease. However, none of these earlier works have addressed the aberrant and pathogenic LMNA splicing observed in HGPS patients because of the lack of an appropriate mouse model. We report herein a genetically modified mouse strain that carries the HGPS mutation. These mice accumulate progerin, present histological and transcriptional alterations characteristic of progeroid models, and phenocopy the main clinical manifestations of human HGPS, including shortened life span and bone and cardiovascular aberrations. By using this animal model, we have developed an antisense morpholinobased therapy that prevents the pathogenic Lmna splicing, dramatically reducing the accumulation of progerin and its associated nuclear defects. Treatment of mutant mice with these morpholinos led to a marked amelioration of their progeroid phenotype and substantially extended their life span, supporting the effectiveness of antisense oligonucleotidebased therapies for treating human diseases of accelerated aging.
Publication Title
Splicing-directed therapy in a new mouse model of human accelerated aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples