Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis.
Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass.
Sex, Age, Specimen part
View SamplesWe previously isolated a subclone, MIN6 clone 4, from the parental MIN6 cells, that shows well-regulated insulin secretion in response to glucose, glybenclamide, and KCl, even after prolonged culture. To investigate the molecular mechanisms responsible for preserving GSIS in this subclone, we compared four groups of MIN6 cells: Pr-LP (parental MIN6, low passage number), Pr-HP (parental MIN6, high passage number), C4-LP (MIN6 clone 4, low passage number), and C4-HP (MIN6 clone 4, high passage number). Based on their capacity for GSIS, we designated the Pr-LP, C4-LP, and C4-HP cells as responder cells. In a DNA microarray analysis, we identified a group of genes with high expression in responder cells (responder genes), but extremely low expression in the Pr-HP cells.
Microarray analysis of novel candidate genes responsible for glucose-stimulated insulin secretion in mouse pancreatic β cell line MIN6.
Cell line
View SamplesThe transcription factor Foxp3 is usually considered the master regulator for the CD4+CD25+ "Treg" lineage, which plays a key role in controlling immune and autoimmune responses, and is characterized by a unique transcriptional signature. We have performed a meta-analysis of this signature in Treg cells in several conditions to delineate the elements that can be ascribed to T cell activation, TGFbeta signaling, or Foxp3 itself. We find that these influences synergize to activate many of the signatures components. Foxp3 and TGFbeta signaling have interconnected relationships, as Foxp3 is induced by TGFbeta while enhancing TGFbetas positive feedback loop. Much of the Treg signature cannot be ascribed to Foxp3, as it contains gene clusters that are co-regulated, but cannot be transactivated, by Foxp3. This suggests that the Treg lineage is specified at a higher level of regulation, upstream of Foxp3, which does control some of the lineages essential immunoregulatory attributes.
Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature.
Age, Specimen part
View SamplesWe identified fibro-inflammatory and keratin gene expression signatures in systemic sclerosis skin.
Dissecting the heterogeneity of skin gene expression patterns in systemic sclerosis.
Age, Specimen part, Race, Subject, Time
View SamplesThis study explored the role of the growth hormone (GH) / insulin-like growth factor 1 (IGF-1) axis on the life-long caloric restriction (CR)-associated remodeling of white adipose tissue (WAT). Adipocyte size and gene expression profiles, using high-density oligonucleotide microarrays, were analyzed in WAT of six- to seven-month old wild Wistar rats fed ad libitum (AL) or subjected to a 30% caloric restriction (CR), and heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (Tg). While not significant in Tg rats, adipocyte size was significantly reduced in CR rats compared with AL rats. The microarray data based on the principal component analysis demonstrated that the gene expression profile of CR rats markedly differed from the AL rats, while Tg hardly differed, suggesting that CR-associated WAT remodeling was predominantly regulated in a GH/IGF-1-independent manner. The gene cluster with the largest change induced by CR included several genes involved in lipid biosynthesis and inflammation. Moreover, many of the genes transcriptionally regulated by sterol regulatory element binding proteins (SREBPs) were found in the cluster related to lipid biosynthesis. Real-time reverse transcription polymerase chain reaction analysis confirmed that the expression of SREBP-1 and its down-stream targets was particularly up-regulated in CR rats compared with SREBP-2 and its down-stream targets. Our findings suggest that SREBP-1 is a major transcription factor in CR-associated remodeling of WAT, and might be one of the key regulators of the anti-aging and pro-longevity effects of CR.
Caloric restriction-associated remodeling of rat white adipose tissue: effects on the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding protein-1, and macrophage infiltration.
Age, Specimen part
View SamplesThe interaction between cancer and stroma plays a key role in tumor progression. Inactivation of p53 is often observed in stromal cells surrounding in cancer, suggesting that p53 in fibroblasts is involved in tumor progression.
TSPAN12 is a critical factor for cancer-fibroblast cell contact-mediated cancer invasion.
Sex, Specimen part, Cell line
View SamplesGene expression is regulated by various mechanisms. One is gene silencing, which is caused by highly condensed chromatin structure. S. pombe Sgo2 is a protein involved in the spindle assembly checkpoint at centromere. In order to investigate the other functions of Sgo2, we analyzed the effect of Sgo2 deletion in global gene expressions.
Shugoshin forms a specialized chromatin domain at subtelomeres that regulates transcription and replication timing.
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View SamplesIn lung cancer progression, p53 mutations are more often observed in invasive tumors than in non-invasive tumors, suggesting that p53 is involved in tumor invasion and metastasis. To understand the nature of p53 function as a tumor suppressor, it is crucial to elucidate the detailed mechanism of the alteration in epithelial cells, the main origin of solid tumors, following p53 inactivation.
TSPAN2 is involved in cell invasion and motility during lung cancer progression.
Sex, Age, Specimen part, Treatment
View SamplesDifferentially expressed genes along the paraxial mesoderm of 12 somite stage zebrafish embryos are identified
Spatiotemporal compartmentalization of key physiological processes during muscle precursor differentiation.
Specimen part
View SamplesThe Drosophila midgut is an ideal model system to study molecular mechanisms that interfere with the intestinal stem cells’ (ISCs) ability to function in tissue homeostasis. Due to the lack of a combination of molecular markers suitable to isolate ISCs from aged intestines, it has been a major challenge to study endogenous molecular changes of ISCs during aging. Our FACS-based approach using the esg-GAL4, UAS-GFP fly line allowed the isolation of a cell population enriched for ISCs from young and old midguts by their small size, little granularity and low GFP intensity. The isolated ISCs were subsequently used for RNA sequencing to identify endogenous changes in the transcriptome of young versus old ISCs. Overall design: Cell populations enriched for ISCs isolated from young (6-8 days old) and old (59-65 days old) midguts were sorted. Cells from three different batches of young and old midguts were subjected to Next Generation Sequencing using Illumina Genome Analyzer IIx.
Nipped-A regulates intestinal stem cell proliferation in <i>Drosophila</i>.
Age, Specimen part, Subject
View Samples