Identification of a NVS-ZP7-3 response signature in T-ALL cell lines to understand the transcriptional response in both Notch pathway active cell lines and Notch pathway inactive lines.
Discovery of a ZIP7 inhibitor from a Notch pathway screen.
Cell line, Treatment
View SamplesSenescence is a developmental process and chlorophyll is an indicator of leaf senescene. In plants cytokinin plays a role in delaying leaf senescence. Chlorophyll degradation is tightly regulated during senescence and cytokinin might interplay in the chrorophyll degradation pathway to regulate leaf greening.
Cytokinin delays dark-induced senescence in rice by maintaining the chlorophyll cycle and photosynthetic complexes.
Specimen part
View SamplesWe describe a case of severe neonatal anemia with kernicterus due to compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1 null human. The phenotype of severe DAT-negative non-spherocytic hemolytic anaemia (NSHA), jaundice, hepato-splenomegaly, and marked erythroblastosis is more severe than that present in CDA type IV due to dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis. Overall design: mRNA sequencing on peripheral blood from a family trio (mother, father and proband) where parents were asymptomatic and proband had severe neonatal anemia.
KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Specimen part
View SamplesImmunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions and its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalyzing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. Using a combination of literature information, transcription factor prediction models and genome-wide expression arrays, we inferred the regulatory network of IRG1 in mouse and human macrophages.
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Specimen part
View SamplesImmunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions and its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalyzing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. Using a combination of literature information, transcription factor prediction models and genome-wide expression arrays, we inferred the regulatory network of IRG1 in mouse and human macrophages.
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Specimen part
View SamplesWe comprehensively explored Fas expression (protein and mRNA) and function in lymphocyte activation, apoptosis, proliferation and transcriptome, using flow cytometry, [3H]-thymidine incorporation and microarray analysis in PBMC from HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) patients.
A Fas<sup>hi</sup> Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation.
Specimen part, Disease stage, Treatment
View SamplesWe used mouse Clariom-S microarrays to study the gene expression profile of ID8 cancer cells stimulated with C-C Chemokine Ligand 6 (CCL6).
Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1.
Specimen part, Cell line
View SamplesWe report a simultaneous comparison of striatal mRNA levels by RNA sequencing mice with graded levels of HD-like abnormalities Overall design: Examination of 4 different mouse lines
Allelic series of Huntington's disease knock-in mice reveals expression discorrelates.
Specimen part, Subject
View SamplesMedullary breast cancers (MBC) display a basal profile, but a favorable prognosis. We hypothesized that a previously published 368-gene expression signature associated with MBC might serve to define a prognostic classifier in basal cancers. We collected public gene expression and histoclinical data of 2145 invasive early breast adenocarcinomas. We developed a Support Vector Machine (SVM) classifier based on this 368-gene list in a learning set, and tested its predictive performances in an independent validation set. Then, we assessed its prognostic value and that of six prognostic signatures for disease-free survival (DFS) in the remaining 2034 samples. The SVM model accurately classified all MBC samples in the learning and validation sets. A total of 466 cases were basal across other sets. The SVM classifier separated them into two subgroups, subgroup 1 (resembling MBC) and subgroup 2 (not resembling MBC). Subgroup 1 exhibited 71% 5-year DFS, whereas subgroup 2 exhibited 50% (p=9.93E-05). The classifier outperformed the classical prognostic variables in multivariate analysis, conferring lesser risk for relapse in subgroup 1 (HR=0.52, p=3.9E-04). This prognostic value was specific to the basal subtype, in which none of the other prognostic signatures was informative.
A gene expression signature identifies two prognostic subgroups of basal breast cancer.
Age, Specimen part
View Samples