Analysis of GPR120 which play roles for the fatty acid sensor in adipose tissue. Results provide insight into the transcriptional effects caused by the loss of the GPR120 proteins and provide further insight into their functions.
Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human.
Specimen part, Treatment, Subject
View SamplesWe report a highly-penetrant form of obesity, initially observed in 31 heterozygous carriers of a 593kb or larger deletion at 16p11.2 from amongst subjects ascertained for cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16053 individuals from 8 European cohorts; such deletions was absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (p = 6.4x10-8, OR = 43). These findings highlight a promising strategy for identifying missing heritability in obesity and other complex traits, in which insights from rare extreme cases can be used to elucidate the basis for more common phenotypes.
A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.
Specimen part, Disease
View SamplesActivity-dependent transcriptional profiling was performed in the basolateral amygdala in order to identify unique genetic markers for functionally distinct neuronal populations
Antagonistic negative and positive neurons of the basolateral amygdala.
No sample metadata fields
View SamplesThe culture of neural stem cells (NSCs) as floating neurospheres has become widely used as an experimental model to analyse the properties of NSCs. Although the neurosphere model has existed for two decades, there is still no standard protocol to grow NSCs in this way. Thus, we have analysed the consequences of the frequency of growth factor (FGF-2 and EGF) addition to embryonic and adult olfactory bulb stem cells (eOBSCs and aOBSCs) cultures, specifically in terms of proliferation, cell cycle progression, death and differentiation, as well as on global changes in gene expression and signaling pathways. We found that addition of FGF-2 and EGF every two or four days rather than daily significantly reduces the volume of the neurospheres and the total number of cells, changes that were more evident in aOBSC than in eOBSC cultures. The reduction in neurosphere size was mainly due to an increase in cell death and occurs without major changes in the cell cycle parameters tested. Moreover, partial deprivation of FGF-2 and EGF produces a mild increase in aOBSC differentiation during the proliferative phase. Remarkably, these effects were accompanied by a significant upregulation in the expression of genes involved in cell death regulation (Cryab), lipid catabolic processes (Pla2g7), cell adhesion (Dscaml1), cell differentiation (Dscaml1, Gpr17, S100b) and signal transduction (Gpr17, Ndrg2), among others. These findings support that continuous supply of FGF-2 and EGF is critical to maintain the viability/survival of NSCs in culture and reveals novel molecular hallmarks of NSC maintenance/survival and expansion in response to these growth factors.
A global transcriptome analysis reveals molecular hallmarks of neural stem cell death, survival, and differentiation in response to partial FGF-2 and EGF deprivation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
LncRNA Expression Discriminates Karyotype and Predicts Survival in B-Lymphoblastic Leukemia.
Specimen part, Disease, Treatment
View SamplesLong non-coding RNAs (lncRNAs) have been found to play a role in gene regulation with dysregulated expression in various cancers. The precise role that lncRNA expression plays in the pathogenesis of B-acute lymphoblastic leukemia (B-ALL) is unknown. Therefore, unbiased microarray profiling was performed on human B-ALL specimens and it was determined that lncRNA expression correlates with cytogenetic abnormalities, which was confirmed by RT-qPCR in a large set of B-ALL cases. Importantly, high expression of BALR-2 correlated with poor overall survival and diminished response to prednisone treatment. In line with a function for this lncRNA in regulating cell survival, BALR-2 knockdown led to reduced proliferation, increased apoptosis, and increased sensitivity to prednisolone treatment. Conversely, overexpression of BALR-2 led to increased cell growth and resistance to prednisone treatment. Interestingly, BALR-2 expression was repressed by prednisolone treatment and its knockdown led to upregulation of the glucocorticoid response pathway in both human and mouse B-cells. Together, these findings indicate that BALR-2 plays a functional role in the pathogenesis and/or clinical responsiveness of B-ALL and that altering the levels of particular lncRNAs may provide a future direction for therapeutic development.
LncRNA Expression Discriminates Karyotype and Predicts Survival in B-Lymphoblastic Leukemia.
Specimen part, Treatment
View SamplesWe examined if pediatric AMLs rank-ordered according to C/EBP expression showed the activation of similar pathways. AML samples were dichotomized into groups including the upper quartile (Q1) and the lower three quartiles (Q2-4) according to their C/EBP expression values. Moreover, AML samples were associated to French-American-British (FAB) classification.
CREB engages C/EBPδ to initiate leukemogenesis.
Specimen part, Disease
View SamplesTo examine the role of CREB overexpression in hematopoiesis, we created a model of leukemia in zebrafish by overexpressing the human CREB in the myeloid hematopoietic lineage. Whole transcriptome analysis of kidney-marrow revealed 171 genes differently expressed between CREB- and control-zebrafish (five per group). Interestingly, the integration of this signature with human deposited data revealed that this tumor resembled a human AML at transcriptome level.
CREB engages C/EBPδ to initiate leukemogenesis.
Specimen part
View SamplesOchratoxin A gene expression profiling in liver and kidney, with time points of exposure from 7 days to 12 motnhs
A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin a carcinogenicity in rat.
No sample metadata fields
View SamplesTo understand the role of MiT in Drosophila, we set out to identify critical gene targets by looking at changes in the WT transcriptome induced by either gain or loss of MiT function. Mutant hindgut and malpighian tubules provided loss-of function tissue and nub-Gal4-driven expression of MiT in the wing epithelium was used for gain-of-function. In the wing disc experiment, 543 genes were upregulated by exogenous MiT, and 359 genes were downregulated (>1.4 fold; P value < 0.01). In the larval HG+MT, 897 genes were downregulated and 898 were upregulated (>1.4 fold; P value < 0.01) after MiT. Among these genes, 85 were both upregulated in wing discs and downregulated in mutant HG+MT, and are the common genes that regulated by MiT in both tissues.
Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1.
Specimen part
View Samples