Transcriptome profiling was performed on muscle biopsies from patients immediately before Total Knee Arthroplasty and two hours after TKA and tourniquet application. Overall design: RNA was isolated from 10 patients who were give vastus lateralis muscle biopsies immediately before surgery and 2 hours post surgery with tourniquet
Transcriptional profiling and muscle cross-section analysis reveal signs of ischemia reperfusion injury following total knee arthroplasty with tourniquet.
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View SamplesEffects of the pan-anti-apoptotic BCL-2 family small molecule inhibitor, obatoclax mesylate (GeminX Pharmaceuticals), on gene expression were evaluated by microarray analysis in order to gain insights into the killing mechanism by this compound in two human MLL-AF4 cell lines. The results of the gene expression profiling substantiated other lines of evidence derived from genetic and chemical cell death pathway inhibition, Western blot analysis, flow cytometric apoptosis assays, and electron microscopic analyses, showing triple apoptosis, autophagy, and necroptosis death pathway activation by this agent. The results also demonstrated modulation of a number of novel targets of obatoclax encoding various cell death factors at the gene expression level.
Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia.
Cell line
View SamplesGene expression profiling was performed on 97 cases of infant ALL from Children's Oncology Group Trial P9407. Statistical modeling of an outcome predictor revealed 3 genes highly predictive of event-free survival (EFS), beyond age and MLL status: FLT3, IRX2, and TACC2. Low FLT3 expression was found in a group of infants with excellent outcome (n = 11; 5-year EFS of 100%), whereas differential expression of IRX2 and TACC2 partitioned the remaining infants into 2 groups with significantly different survivals (5-year EFS of 16% vs 64%; P < .001). When infants with MLL-AFF1 were analyzed separately, a 7-gene classifier was developed that split them into 2 distinct groups with significantly different outcomes (5-year EFS of 20% vs 65%; P < .001). In this classifier, elevated expression of NEGR1 was associated with better EFS, whereas IRX2, EPS8, and TPD52 expression were correlated with worse outcome. This classifier also predicted EFS in an independent infant ALL cohort from the Interfant-99 trial. When evaluating expression profiles as a continuous variable relative to patient age, we further identified striking differences in profiles in infants less than or equal to 90 days of age and those more than 90 days of age. These age-related patterns suggest different mechanisms of leukemogenesis and may underlie the differential outcomes historically seen in these age groups.
Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: a Children's Oncology Group study.
Sex, Age, Specimen part, Treatment, Race
View SamplesWe and others have previously observed that adipocytes and preadipocytes taken from different adipose tissue depots are characterized by differential expression of developmental and patterning genes (Dankel et al., 2010; Ferrer-Lorente et al., 2014; Gesta et al., 2006; Lee et al., 2017a; Lee et al., 2013; Macotela et al., 2012; Tchkonia et al., 2007; Yamamoto et al., 2010). To investigate how adipocyte heterogeneity and differences in the expression of developmental genes might impact the biology of adipocytes and preadipocytes, we created preadipocyte cell lines from the stromovascular fraction (SVF) isolated from the scapular white, inguinal, perigonadal, perirenal, and mesenteric fat pads of 6-week old male Immortomouse (Jat et al., 1991).During routine culture of the subcutaneous and visceral/perigonadal clonal cell lines, we observed extreme variation in media acidification rates that was unrelated to the fat pad of origin, the differentiation capacity of the cells, or the rate of their proliferation, suggesting metabolic heterogeneity. To further investigate this possibility, 24 clonal cell lines (12 each from subcutaneous and perigonadal fat) were selected based on variable media acidification rates, and their mRNA expression pattern determined by microarray analysis. The expression data was clustered using three different algorythms, and the consensus was used to categorize each type of adipose tissue.
Developmental and functional heterogeneity of white adipocytes within a single fat depot.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Specimen part, Cell line, Treatment
View SamplesAlternative splicing analysis after treatment with three clinically aproved drugs
Rapid-response splicing reporter screens identify differential regulators of constitutive and alternative splicing.
Cell line, Treatment
View SamplesArs2 is a component of the nuclear cap-binding complex that is required for cellular proliferation and contributes to microRNA biogenesis. Arrays were performed to determine the repertoire of genes that change following knock-down of Ars2. Knock-down of DGCR8 was also performed to determine which changes in Ars2 knock-down cells resulted from defects in microRNA expression.
Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Specimen part, Cell line, Treatment
View SamplesWe investigated the differential regulation patterns of type I anti-CD20 monoclonal antibody (mAb) rituximab and type II obinutuzumab on a transcriptional level. Using a panel of MCL cell lines, we determined the effects of obinutuzumab and rituximab as monotherapies as well as in combination on cell viability and proliferation.
Differential regulation patterns of the anti-CD20 antibodies obinutuzumab and rituximab in mantle cell lymphoma.
Specimen part, Cell line
View SamplesIt has been known for some time that muscle repair potential becomes increasingly compromised with advancing age, and that this age-related defect is associated with reduced activity of muscle satellite cells and with the presence of chronic, low grade inflammation in the muscle. Working from the hypothesis that a heightened inflammatory tone in aged muscle could contribute to poor regenerative capacity, we developed genetic systems to inducibly alter inflammatory gene expression in satellite cells or muscle fibers by modulation of the activity of nuclear factor B (NF-B), a master transcriptional regulator of inflammation whose activity is upregulated in many cell types and tissues with age. These studies revealed that activation of NF-B activity in muscle fibers, but not in satellite cells, drives muscle dysfunction and that lifelong inhibition of NF-B activity in myofibers preserves muscle regenerative potential with aging via cell-non-autonomous effects on satellite cell function. Further analysis of differential gene expression in muscles with varying NF-B activity identified a secreted phospholipase (PLA2G5) as a myofiber-expressed NF-B-regulated gene that governs muscle regenerative capacity with age. Together, these data suggest a model in which NF-B activation in muscle fibers increases PLA2G5 expression and drives the impairment in regenerative function characteristic of aged muscle. Importantly, inhibition of NF-B function reverses this impairment, suggesting that FDA-approved drugs, like salsalate, a prodrug form of sodium salicylate, may provide new therapeutic avenues for elderly patients with reduced capacity to recover effectively from muscle injury.
Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function.
Age
View SamplesThis project looks into experimentally identifying all minor introns by knocking down the minor spliceosome''s catalytic snRNP, U6atac. Overall design: Knockdown of U6atac by antisense morpholino followed by examining mRNA splicing by RNA-seq
Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA.
Specimen part, Cell line, Subject
View Samples