We 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 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 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.
No sample metadata fields
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 SamplesCardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell-type in terms of their origins and functional effects in vivo. Methods: Here we generate Postn (periostin) gene-targeted mice containing a tamoxifen inducible Cre for cellular lineage tracing analysis. This Postn allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Results: Lineage tracing with 4 additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin+ myofibroblasts reduces collagen production and scar formation after myocardial infarction. Periostin-traced myofibroblasts also revert back to a less activated state upon injury resolution. Conclusions: Our results define the myofibroblast as a periostin-expressing cell-type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21+ tissue-resident fibroblasts. Overall design: Fluidigm C1 whole genome transcriptome analysis of lineage mapped cardiac myofibroblasts
Genetic lineage tracing defines myofibroblast origin and function in the injured heart.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Cell line, Treatment
View SamplesContinuous sperm production is not necessary for the survival of the organism, but is essential to maintain a species. The process of spermatogenesis is comprised of three phases: mitotic proliferation, meiosis, and spermiogenesis. To illuminate germline intrinsic and extrinsic programs, we performed single-cell RNA sequencing on ~35K cells from the adult mouse testis. This analysis provides a comprehensive molecular atlas of the testis, identifying both known and novel cell types. We demonstrate for the first time the continuous nature of germ cell differentiation, provide molecular signatures and subtype-specific molecular markers, and identify several novel candidate regulators of spermatogenesis. Finally, we demonstrate in vivo using spatial mapping that germ and somatic cell molecular subtypes correspond to previously defined histological cell types residing at different stages of seminiferous epithelial cycle. Taken together, our results unveil the complexity of the testis, and provide a global, unbiased roadmap of the in vivo gametogenesis program. Overall design: Drop-seq of whole mouse testis and enriched populations. NOTE: As the initial submission of raw data only included partial run (extracted mouse cells) for some samples, all raw data for the following samples have been replaced to include the complete/original run for each sample (Feb 2019): GSM3069439, GSM3069440, GSM3069443-GSM3069448,GSM3069450, GSM3069451, GSM3069459-GSM3069463 All raw data for the 25 samples are paired-end, with 8 single-species samples + 17 mixed-species samples. For mixed-species samples, the major species is mouse, and the spike-in can be either human or monkey. The spike-in species were only used to confirm cells are not doublets by two-species mixing experiments, but not analyzed in processed data under GSE112393.
A Comprehensive Roadmap of Murine Spermatogenesis Defined by Single-Cell RNA-Seq.
Age, Specimen part, Cell line, Subject
View Samples