Our hypothesis was that at any given point in time, islets will contain differing populations of beta cells at different stages of their lifecycle, with further changes occurring with metabolic stress and aging. We examined subpopulations of beta cells isolated from MIP-GFP mice on the basis of their insulin transcriptional activity and in their expression of p16Ink4a. In addition, using aging C57Bl/6 mice as a model, markers of beta cell aging were identified and validated: Igf1r and Cd99 expression increased with age, whereas Kcnq5 was decreased with age. These markers were correlated with an age-related decline in function. The functional aging of beta cells was accelerated by S961, an antagonist to the insulin receptor, which induced insulin resistance. Particularly surprising was the finding of marked islet heterogeneity as demonstrated with the marked staining differences of the markers: Igf1r, Cd99 and Kcnq5. These novel findings about beta cell and islet heterogeneity, and how they change with age, open up an entirely new set of questions that must be addressed about the pathogenesis of type 2 diabetes. The present study has identified new markers of aging in beta cells and found that the expression of these and other markers can be increased by insulin resistance. This provides insight into how insulin resistance might accelerate the death of beta cells. In addition, striking heterogeneity among islets was found, which opens up new ways to think about islet biology and the pathogenesis of T2D.
β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance.
Age, Specimen part
View SamplesWe performed microarrays to identify change of gene expression under NR, CR, and RM and found differentially expressed genes between each condition.
Caloric Restriction and Rapamycin Differentially Alter Energy Metabolism in Yeast.
No sample metadata fields
View SamplesMost human tumors have abnormal numbers of chromosomes, a condition known as aneuploidy. The mitotic checkpoint is an important mechanism that prevents aneuploidy through restraining the activity of the anaphase-promoting complex (APC). USP44 was identified as a key regulator of APC activation that maintains the association of MAD2 with the APC co-activator Cdc20. However, the physiological importance of USP44 and its impact on cancer biology are unknown. Here, we show that USP44 is required to prevent tumors in mice and is frequently down-regulated in human lung cancer. USP44 inhibits chromosome segregation errors independently of its role in the mitotic checkpoint by regulating proper centrosome separation, positioning, and mitotic spindle geometry, functions that require direct binding to the centriole protein, centrin. These data reveal a new role for the ubiquitin system in mitotic spindle regulation and underscore the importance of USP44 in the pathogenesis of human cancer.
USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis.
Sex, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer.
No sample metadata fields
View SamplesExpression data were used to predict the activity status of diverse pathways, which were compared to Tamoxifen response
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer.
No sample metadata fields
View SamplesExpression data were used to predict the activity status of diverse pathways, which were compared to Tamoxifen response
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer.
No sample metadata fields
View SamplesWe used microarrays to compare gene expression across different murine tissues.
Using ribosomal protein genes as reference: a tale of caution.
No sample metadata fields
View SamplesCrossing of hDMD mice that contain the full-length 2.3 Mb hDMD gene were crossed with dystrophin-deficient mdx mice and dystrophin and utrophin double-deficient mdx x utrn-/- mice resulted in a full rescue of the dystrophic features of these mice, as concluded from histological analysis. Analysis on Affymetrix gene chips demonstrated that also expression profiles of the dystrophic mice were normalized by crossing with transgenic hDMD mice. This confirms the full functionality of the hDMD transgene in mice.
Generation and characterization of transgenic mice with the full-length human DMD gene.
No sample metadata fields
View SamplesBy means of 3' end sequencing we provide a genome-wide, high-resolution polyadenylation map of the human heart. By sequencing 5 control en 5 dilated cardiomyopathy (DCM) myocardial specimens we investigate the difference in alternative polyadenylation (APA) in healthy and diseased hearts.
Genome-Wide Polyadenylation Maps Reveal Dynamic mRNA 3'-End Formation in the Failing Human Heart.
No sample metadata fields
View SamplesThe functioning of a specific tissue depends on the expression pattern of the different genes. We used microarrays to compare gene expression across different murine tissues, to get a better understanding in the expression pattern and functioning of the different tissues. With this analysis, we were not only able to identify genes that were specifically expressed in a spicific tissue but, as important, we also identified genes that were specifically repressed in a tissue, compared to al the other analysed tissues.
Tissue-specific disallowance of housekeeping genes: the other face of cell differentiation.
Sex, Specimen part
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