How chromatin controls transcription elongation and splicing is an open question. Here we determine the transcriptomic changes of cells partially depleted of core histones. For that we construct a cell line with Doxycycline-controlled levels of the histone regulatory protein SLBP (HCT-shSLBP). HCT-shSLBP is derived from the human colon cancer cell line HCT116.
Defective histone supply causes changes in RNA polymerase II elongation rate and cotranscriptional pre-mRNA splicing.
Specimen part, Cell line
View SamplesTo identify signature genes that help distinguish (1) sepsis from non-infectious causes of systemic inflammatory response syndrome, (2) between Gram-positive and Gram-negative sepsis.
Gene-expression profiling of peripheral blood mononuclear cells in sepsis.
No sample metadata fields
View SamplesOsteoarthritis (OA) is a degenerative joint disease that involves destruction of articular cartilage and eventually leads to disability. Mesenchymal stem cells (MSCs) reside in healthy and diseased cartilage, and through their chondrogenic potential may provide a strategy for cartilage repair. To this end, we performed an image-based, high throughput screen and identified the small molecule, kartogenin, that promotes selective MSC differentiation into chondrocytes (EC50=100nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A and induces chondrogenesis by regulating the CBFbeta-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to an effective stem-cell based therapy for osteoarthritis.
A stem cell-based approach to cartilage repair.
Specimen part
View SamplesWe introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multigenerationa lineage tracking under controlled culture conditions. Overall design: Examination of lineage and cell cycle dependent transcriptional profiles in two cell types
A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages.
Specimen part, Cell line, Subject
View SamplesRationale: Lipopolysaccharide (LPS) is ubiquitous in the environment. Inhalation of LPS has been implicated in the pathogenesis and/or severity of several lung diseases, including pneumonia, chronic obstructive pulmonary disease and asthma. Alveolar macrophages are the main resident leukocytes exposed to inhaled antigens. Objectives: To obtain insight into which innate immune pathways become activated within human alveolar macrophages upon exposure to LPS in vivo.
Gene expression profiles in alveolar macrophages induced by lipopolysaccharide in humans.
Sex, Specimen part, Treatment, Subject
View SamplesWe compared human female hiPSC lines (all derived from IMR-90 fibroblasts) that were XIST RNA-positive and XIST RNA-negative. We also examined the gene expression patterns for 2 female hIPSCs (derived from different disease model fibroblasts) that were also negative for XIST RNA. hiPS 12D-1 is derived from Huntington's Disease patient and 6C-1 is derived from a Type I Diabetes Mellitus patient (Park et al Nature 2008).
Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes.
Specimen part
View SamplesExpression data from valvular interstitial cells cultured in 2D or 3D PEG hydrogel systems compared to culture on tissue culture polystyrene and freshly isolated cells
Transcriptional profiles of valvular interstitial cells cultured on tissue culture polystyrene, on 2D hydrogels, or within 3D hydrogels.
Specimen part
View SamplesPrevious studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001). Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
A protease-resistant PML-RAR{alpha} has increased leukemogenic potential in a murine model of acute promyelocytic leukemia.
Cell line
View SamplesMouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. This gives us an opportunity to isolate the genetic aspect of variation in expression and compare it to other phenotypic variables. We have investigated these issues using an eight-strain expression profile comparison with four replicates per strain on Affymetrix MGU74av2 GeneChips focusing on one well-defined brain tissue (the hippocampus). We identified substantial strain-specific variation in hippocampal gene expression, with more than two hundred genes showing strain differences by a very conservative criterion. Many such genetically driven differences in gene expression are likely to result in functional differences including differences in behaviour. A large panel of inbred strains could be used to identify genes functionally involved in particular phenotypes, similar to genetic correlation. The genetic correlation between expression profiles and function is potentially very powerful, especially given the current large-scale generation of phenotypic data on multiple strains (the Mouse Phenome Project). As an example, the strongest genetic correlation between more than 200 probe sets showing significant differences among our eight inbred strains and a ranking of these strains by aggression phenotype was found for Comt, a gene known to be involved in aggression.
Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviour.
No sample metadata fields
View SamplesThe accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) causes stress and induces the unfolded protein response (UPR) which is characterised in part by the transcriptional induction of genes involved in assisting protein folding. Translational responses to ER stress have been less well described and here we report on a genome-wide analysis of translational regulation in the response to the ER stress-inducing agent dithiothreitol (DTT) in Saccharomyces cerevisiae. Although the observed polysome profiles were similar under control and ER stress conditions microarray analysis identified transcipt-specific translational regulation. Genes with functions in ribosomal biogenesis and assembly were translationally repressed under ER stress. In contrast mRNAs for known UPR genes, including the UPR transcription factor HAC1, the ER-oxidoreductase ERO1 and the ER-associated protein degradation (ERAD) gene DER1 were enriched in polysomal fractions under ER stress conditions. In addition, we show that splicing of HAC1 mRNA is required for efficient ribosomal loading and that Gcn2p is required for normal HAC1 splicing, so shedding light on the role of this protein kinase in the UPR pathway.
Transcript-specific translational regulation in the unfolded protein response of Saccharomyces cerevisiae.
No sample metadata fields
View Samples