This SuperSeries is composed of the SubSeries listed below.
Inhibition of Endothelial NOTCH1 Signaling Attenuates Inflammation by Reducing Cytokine-Mediated Histone Acetylation at Inflammatory Enhancers.
Specimen part
View SamplesNotch1 is a key regulator of endothelial cell behaviour. This experiment was designed to identify genes regulated by Notch1 signaling in inflammatory activated mouse endothelial cells.
Inhibition of Endothelial NOTCH1 Signaling Attenuates Inflammation by Reducing Cytokine-Mediated Histone Acetylation at Inflammatory Enhancers.
Specimen part
View SamplesProinflammatory activation of endothelial cells leads to recruitment of leukocytes by upregulation of adhesion molecules and presentation of chemoattractants. In response to such activation there is also a strong shift in the endothelial expression of Notch ligands, with downregulation of Dll4 and a upregulation of JAG1. To assess whether Jagged1 would affect the endothelial activation profile, we suppressed JAG1 expression during IL-1-induced activation by means of siRNA and performed a genome-wide transcriptome analysis. Our results show for the first time that Jagged1 modulates the transcription profile of activated endothelial cells and describe data that imply a role for Jagged1 in sharpening the inflammatory profile of the vasculature, giving it an edge towards leukocyte recruitment. These findings imply that Jagged1 might be a potential therapeutic target to attenuate inflammation and reduce tissue damage in inflammatory diseases.
Inhibition of Endothelial NOTCH1 Signaling Attenuates Inflammation by Reducing Cytokine-Mediated Histone Acetylation at Inflammatory Enhancers.
Specimen part
View SamplesInflammatory activation of endothelial cells enables leukocyte recruitment to tissues. We here investigate how Notch1 signaling affects the transcriptional profile of inflammatory activated human umbilical vein cells.
Inhibition of Endothelial NOTCH1 Signaling Attenuates Inflammation by Reducing Cytokine-Mediated Histone Acetylation at Inflammatory Enhancers.
Specimen part
View SamplesWe Report the genome-wide RNA expression levels in control and schizophrenia hiPSC dervied NPC treated with neuronal media for 2 days. In total about 15,000 gene expression were detected in all samples, of which 1349 were dysregualted. Overall design: Examination, identification and comparision of mRNA expression profliles in control and schizophrenia npc
Common developmental genome deprogramming in schizophrenia - Role of Integrative Nuclear FGFR1 Signaling (INFS).
Specimen part, Subject
View SamplesSarcoidosis + Follow-up 6 month after
Functional genomics and prognosis in sarcoidosis--the critical role of antigen presentation.
No sample metadata fields
View SamplesSamples collected from human subjects in clinical trials possess a level of complexity, arising from multiple cell types, that can obfuscate the analysis of data derived from them. Blood, for example, contains many different cell types that are derived from a distinct lineage and carry out a different immunological purpose. Failure to identify, quantify, and incorporate sources of heterogeneity into an analysis can have widespread and detrimental effects on subsequent statistical studies.
Optimal deconvolution of transcriptional profiling data using quadratic programming with application to complex clinical blood samples.
Sex, Specimen part
View SamplesA LysM Receptor-like Kinase Mediates Chitin Perception and Fungal Resistance in Arabidopsis
A LysM receptor-like kinase plays a critical role in chitin signaling and fungal resistance in Arabidopsis.
No sample metadata fields
View SamplesExpression of meningioma 1 (MN1) has been proposed to be a negative prognostic molecular marker in adult AML with normal cytogenetics, however its role in pediatric leukemia is unknown. We found elevated MN1 expression in 53 of 88 pediatric leukemia cases: significant amounts of MN1 were found in immature B-cell ALL and most cases of infant leukemia but no MN1 expression was detected in T-cell acute lymphoblastic leukemia (T-ALL). Interestingly 17 of 19 cases harboring MLL-X fusions showed also elevated MN1 expression. Lentiviral siRNA mediated MN1 knock-down resulted in cell cycle arrest and impaired clonogenic growth of 3 MLL-X-positive human leukemia cell lines overexpressing MN1 (THP-1, RS4;11, MOLM13). In a mouse MLL/ENL-induced leukemia MN1 overexpression resulted from retroviral provirus insertion. Strikingly co-expression of MN1 with MLL/ENL resulted in significantly reduced latency for induction of an AML phenotype in mice suggesting functional cooperation. MN1 overexpression in MLL/ENL-carrying cells resulted in expansion of the L-GMP population and facilitated disease induction in secondary recipients. Gene expression profiling allowed to define a number of potential MN1 hematopoietic targets. Up-regulation of CD34, FLT3, HLF, or DLK1 was validated in bone marrow transiently overexpressing MN1, in MN1-induced mouse leukemias, as well as in some cases of pediatric leukemias overexpressing MN1. Taken together, our work suggests that MN1 overexpression is essential for growth of leukemic cells, and that MN1 can act as a cooperating oncogene with MLL-X fusion genes most probably through modification of a distinct gene expression program that leads to expansion of a leukemia initiating cell population.
Functional characterization of high levels of meningioma 1 as collaborating oncogene in acute leukemia.
No sample metadata fields
View SamplesMessenger RNA levels in eukaryotes are balanced by two consecutive regulatory layers. Primary, transcriptional regulation at the level of chromatin and secondary, post-transcriptional regulation of the initial transcript in the cytoplasm. Each layer is individually studied in mechanistic detail, while integration of both processes is required to quantify the individual contribution to steady-state RNA levels. Here we show that chromatin features are sufficient to model transcription rate but with different sensitivities in dividing versus post mitotic cells. In both cases chromatin derived transcript levels explains over 80% of variance in measured RNA level enabling to separate transcription from different post-transcriptional processes. By further inclusion of measurements of mRNA half-life and micro RNA expression data we identify a low quantitative contribution of RNA decay by either micro RNA or general differential turnover to final mRNA levels. Together this establishes a chromatin based quantitative model for the contribution of transcriptional and posttranscriptional processes to steady-state levels of messenger RNA.
Chromatin measurements reveal contributions of synthesis and decay to steady-state mRNA levels.
Specimen part, Disease, Treatment, Time
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