Coordinated BCR-ABL1 kinase-dependent and -independent mechanisms convert p27 from a nuclear tumor suppressor to a cytoplasmic oncogene. Persistence of oncogenic p27 functions despite effective inhibition of BCR-ABL1 may contribute to resistance to tyrosine kinase inhibitors. Overall design: BCR-ABL1 induced p27 versus knockout, controlling with Empty vector p27 versus knock out
BCR-ABL1 promotes leukemia by converting p27 into a cytoplasmic oncoprotein.
No sample metadata fields
View SamplesHuman cytotrophoblast organoid cultures were established from the villous trophoblast of first trimester placentas. We analyzed the global expression profile of the cytotrophoblast organoids (CTB-ORG) and compared to the profile of the tissue of origin i.e. villous cytotrophoblast (vCTB) as well as to differentiated syncytiotrophoblast (STB) and placental fibroblasts (FIB). Overall design: We employed QuantSeq method to analyzed the global expression profile of the cytotrophoblast organoids (4 replicates, CTB-ORG 1-4) and compared to the profile of the tissue of origin i.e. villous cytotrophoblast (3 replicates, vCTB 1-3) as well as to in vitro differentiated syncytiotrophoblast (3 replicates, STB1-3) and placental fibroblasts (2 replicates, FIB 1-2).
Self-Renewing Trophoblast Organoids Recapitulate the Developmental Program of the Early Human Placenta.
Specimen part, Subject
View SamplesTo understand the transcriptional program by which GR regulates skin development, we performed a microarray analysis using the skin of E18.5 GR-/- and GR+/+ mouse embryos.
Glucocorticoid receptor regulates overlapping and differential gene subsets in developing and adult skin.
Specimen part
View SamplesWe report liver transcript profiling by RNA sequencing of Atp7b-/- and wild type mice at six weeks of age. Transcriptional network analysis of RNA-seq data reveals a highly interconnected network of transcriptional activators with over-representation of zinc-dependent and zinc-responsive transcription factors. Overall design: Wild type and Atp7b-/- Mice were maintained on strain C57BL x 129S6/SvEv. Housing was in shoebox cages and fed Mazuri Rodent diet (PMI Nutrition, Inc., Richmond, Indiana), containing 16 ppm Cu, 100 ppm Zn, and 235 ppm Fe and water ad libitum, with a 12-hour light/dark cycle. Six-week-old mice of both sexes were used for transcriptomic studies. Animals were sacrificed by carbon dioxide asphyxiation and liver tissue was harvested for RNA isolation. RNA sequencing was performed at the National Center for Genome Resources (NCGR) using the GAIIx platform. Average read quality was 38. An initial dataset was generated using two wild type and two Atp7b-/- samples with singleton 1x54 runs with 15,823,058; 8,149,631; 22,931,967 and 9,538,147 reads. A second paired end (2x54) dataset was generated to augment the initial singleton dataset with one wild type and one Atp7b-/- run resulting in 36,360,686 and 38,366,743 reads, respectively.
Altered zinc balance in the Atp7b<sup>-/-</sup> mouse reveals a mechanism of copper toxicity in Wilson disease.
Sex, Specimen part, Cell line, Subject
View SamplesTwo 96-well plates per genotype wild type and Myd88 knockout, 4 hour time series in 0.5 hr increments Overall design: Myd88 BMDM transcriptional profiling to complement TF-seq data
Simultaneous Pathway Activity Inference and Gene Expression Analysis Using RNA Sequencing.
Sex, Age, Specimen part, Cell line, Treatment, Subject, Time
View SamplesBone marrow derived macrophages treated with small molecules and stimulated with LPS Overall design: Wild-type BMDMs pretreated with small molecules for 30 minutes prior to stimulation with LPS
Simultaneous Pathway Activity Inference and Gene Expression Analysis Using RNA Sequencing.
Sex, Age, Specimen part, Cell line, Treatment, Subject, Time
View SamplesBone marrow derived macrophages treated with small molecules and stimulated with LPS Overall design: Wild-type BMDMs pretreated with small molecules for 30 minutes prior to stimulation with LPS
Simultaneous Pathway Activity Inference and Gene Expression Analysis Using RNA Sequencing.
Sex, Age, Specimen part, Cell line, Treatment, Subject
View SamplesParkinson disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein (SNCA) and other proteins in aggregates termed “Lewy Bodies” within neurons. PD has both genetic and environmental risk factors, and while processes leading to aberrant protein aggregation are unknown, past work points to abnormal levels of SNCA and other proteins. Although several genome-wide studies have been performed for PD, these have focused on DNA sequence variants by genome-wide association studies (GWAS) and on RNA levels (microarray transcriptomics), while genome-wide proteomics analysis has been lacking. After appropriate filters, proteomics identified 3,558 unique proteins and 283 of these (7.9%) were significantly different between PD and controls (q-value<0.05). RNA-sequencing identified 17,580 protein-coding genes and 1,095 of these (6.2%) were significantly different (FDR p-value<0.05), but only 166 of the FDR significant protein-coding genes (0.94%) were present among the 3,558 proteins characterized. Of these 166, eight genes (4.8%) were significant in both studies, with the same direction of effect. Functional enrichment analysis of the proteomics results strongly supports mitochondrial-related pathways, while comparable analysis of the RNA-sequencing results implicates protein folding pathways and metallothioneins. Ten of the implicated genes or proteins co-localized to GWAS loci. Evidence implicating SNCA was stronger in proteomics than in RNA-sequencing analyses. Notably, differentially expressed protein-coding genes were more likely to not be characterized in the proteomics analysis, which lessens the ability to compare across platforms. Combining multiple genome-wide platforms offers novel insights into the pathological processes responsible for this disease by identifying pathways implicated across methodologies. Overall design: The study consists of mRNA-Seq (29 PD, 44 neurologically normal controls) and three-stage Mass Spectrometry Tandem Mass Tag Proteomics (12 PD, 12 neurologically normal controls) performed in post-mortem BA9 brain tissue. The proteomics samples are a subset of the RNA-Seq samples.
Integrative analyses of proteomics and RNA transcriptomics implicate mitochondrial processes, protein folding pathways and GWAS loci in Parkinson disease.
No sample metadata fields
View SamplesMaternal obesity can program metabolic syndrome in offspring but the mechanisms are not well characterized. Moreover, the consequences of maternal overnutrition in the absence of frank obesity remain poorly understood. This study aimed to determine the effects of maternal consumption of a high fat-sucrose diet on the skeletal muscle metabolic and transcriptional profiles of adult offspring. Female Sprague Dawley rats were fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. Although maternal weights were not different between groups at conception or weaning, HFD dams were ~22% heavier than chow fed dams from mid-pregnancy until 4 days post-partum. Adult male offspring of HFD dams were not heavier than controls but demonstrated features of insulin resistance including elevated plasma insulin concentration (+40%, P<0.05). Next Generation mRNA Sequencing was used to identify differentially expressed genes in the soleus muscle of offspring, and Gene Set Enrichment Analysis (GSEA) to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 pathways enriched for up-regulated genes, including cytokine signaling (P<0.005), starch and sucrose metabolism (P<0.017), and inflammatory response (P<0.024). A further 8 pathways were significantly enriched for down-regulated genes including oxidative phosphorylation (P<0.004) and electron transport (P<0.022). Western blots confirmed a ~60% reduction in the phosphorylation of the insulin signaling protein Akt (P<0.05) and ~70% reduction in mitochondrial complexes II (P<0.05) and V expression (P<0.05). On a normal diet, offspring of HFD dams developed an insulin resistant phenotype, with transcriptional evidence of muscle cytokine activation, inflammation and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of pre-pregnancy obesity can promote metabolic dysregulation and predispose offspring to type 2 diabetes. Overall design: Messenger RNA profile of skeletal muscle of male offspring from female Sprague Dawley rats fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. There were 5 HFD samples compared to 6 NFD control samples.
Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring.
No sample metadata fields
View SamplesLymphoid committed CD34+lin-CD10+CD24- progenitors undergo a rebound at month 3 after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the absence of acute graft-versus-host disease (aGVHD). Here, we analyzed transcriptional programs of cell-sorted circulating lymphoid committed progenitors and CD34+Lin-CD10- non lymphoid progenitors in 11 allo-HSCT patients having (n=5) or not developed (n=6) grade 2 or 3 aGVHD and in 7 age-matched healthy donors. Major deregulated pathways included protein synthesis, energy production, cell cycle regulation and cytoskeleton organization. Notably, genes from protein biogenesis, translation machinery and cell cycle (CDK6) were over-expressed in progenitors from patients in the absence of aGVHD compared with healthy donors and patients affected by aGVHD. Expression of many genes from the mitochondrial oxidative phosphorylation metabolic pathway leading to ATP production were more specifically increased in lymphoid committed progenitors in absence of aGVHD. This was also the case for genes involved in cell mobilization such as those regulating Rho GTPases activity. In all, we show that circulating lymphoid committed progenitors undergo profound changes in metabolism favoring cell proliferation, energy production and cell mobilization after allo-HSCT in humans. These mechanisms are abolished in case of aGVHD or its treatment, indicating a persistent cell-intrinsic defect after exit from bone marrow.
Alterations of circulating lymphoid committed progenitor cellular metabolism after allogeneic stem cell transplantation in humans.
Disease, Disease stage, Subject
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