Hepatic stellate cells (HSC) are the main stromal cell component of the liver. In healthy liver, quiescent HSC participate in the homeostasis of extracellular matrix (ECM) and store vitamin A. Liver injury causes HSC activation, where they participate in the wound-healing response, by producing ECM components as well as cytokines involved in liver regeneration and inflammation. Moreover, HSC are the main cell type responsible for fibrosis progression. The lack of homogeneous cultures and renewable sources of human HSC has limited the studies of the role of HSC in liver injury, repair anf fibrosis. Here we report a procedure to direct the differentiation of human pluripotent stem cells (PSC) to HSC. The HSClike population (iPS-HSC) was enriched in PDGFR positive cells that expressed key HSC markers. Whole genome transcriptomic analysis revealed that iPS-HSC displayed features intermediate to quiescent and activated HSC. Functional analysis demonstrated that iPS-HSC accumulated retinyl esters into lipid droplets and responded to injury mediators. Moreover, when cultured with HepaRG hepatocytes as aggregates, iPS-HSC support long-term hepatocyte metabolic function and respond to hepatocyte toxicity by activating and promoting organoid fibrogenesis.
Generation of Hepatic Stellate Cells from Human Pluripotent Stem Cells Enables In Vitro Modeling of Liver Fibrosis.
Specimen part
View SamplesYAP is an oncogene and an inducer of Epithelial-to-Mesenchymal Transition (EMT).
Negative regulation of YAP by LATS1 underscores evolutionary conservation of the Drosophila Hippo pathway.
No sample metadata fields
View SamplesTumor hypoxia is associated with poor patient outcome and resistance to therapy. It is associated with a rapid decline in protein production mediated through mTOR signalling. Here we show that it also leads to widespread changes in splicing and a global shift towards the expression of noncoding isoforms, thus providing a novel and orthogonal mechanism by which cells can modulate protein expression. Overall design: Examination of mRNA levels in HCT116 cells after 0 hr, 1 hr, 2 hr and 24 hr in hypoxia. Three biological replicates each.
Hypoxia-driven splicing into noncoding isoforms regulates the DNA damage response.
Specimen part, Cell line, Treatment, Subject, Time
View SamplesT-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL) and are often thought to represent a spectrum of a single disease. The malignant cells in T-ALL and T-LL are morphologically indistinguishable, and they share the expression of common cell surface antigens and cytogenetic characteristics. However, despite these similarities, differences in the predominant sites of disease in T-ALL and T-LL are observed. To determine if underlying biological distinctions may potentially contribute to some of these differences, we analyzed the global gene expression profiles of malignant T-cell precursors in ten T-ALL and nine T-LL using DNA arrays. Ten additional B-precursor ALL bone marrow samples, were used in a separate analysis.
Gene expression profiling reveals intrinsic differences between T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.
No sample metadata fields
View SamplesEstablishment of a transcriptomic profile of human cells treated with genistein with particular emphasis on the assessment of the role of this isoflavone in regulation of expression of psoriasis-related genes stands for the present study. The hypothesis tested was that genistein modulates activity of psoriasis-related genes, by reducing the expression efficiency of genes revealing enhanced activity in psoriatic cells, and by stimulating the expression efficiency of genes revealing decreased activity in psoriatic cells. Results provide important information concerning the extent of action of genistein at the molecular level in terms of modulation of gene expression by this substance.
Molecular action of isoflavone genistein in the human epithelial cell line HaCaT.
Specimen part, Cell line
View SamplesEstablishment of a transcriptomic profile of human cells treated with kaemferol, daidzein, kaemferol/genistein, or daidzein/genistein with particular emphasis on signature of genes coding for enzymes involved in glycosaminoglycan synthesis stands for the present study. The hypothesis tested was that kaemferol, daidzein, kaemferol/genistein, and daidzein/genistein influence expression of some genes, among which are those coding for enzymes required for the synthesis of different GAGs being pathologically accumulated in mucopolysaccharidoses. Results provide important information concerning the extent of action of kaemferol, daidzein, kaemferol/genistein, and daidzein/genistein at the molecular level in terms of modulation of gene expression.
Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids.
Specimen part, Cell line, Treatment
View SamplesThe Saccharomyces cerevisiae R2TP protein complex consists of Rvb1, Rvb2, Pih1 and Tah1. The R2TP complex has been implicated in various cellular processes such as assembly of snoRNP complex, RNA polymerase II complex, apoptosis and PIKK signaling. The involvement of R2TP in assembling various complexes seems to be in part due to Pih1 and Tah1, which serve as adapter/recruiter proteins. Here, we have performed high resolution RNA-seq. analyses to identify differential expression levels between wild type and PIH1 and TAH1 deletion strains of Saccharomyces cerevisiae that can help in unraveling other functions of Pih1 and Tah1. Both wild type and deletion strains contained TAP (tandem affinity purification) tag at the C-terminal end of either RVB1 or RVB2. Overall design: 3 biological replicates were performed for each strains
Proteomic and Genomic Analyses of the Rvb1 and Rvb2 Interaction Network upon Deletion of R2TP Complex Components.
Cell line, Subject
View SamplesWe report the application of RNA sequencing technology for high-throughput profiling of gene expression responses to human rhinovirus infection at 24 hours in air-liquid interface human airway epithelial cell cultures derived from 6 asthmatic and 6 non-asthmatic donors. RNA-seq analysis identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1), and novel ones that were identified for the first time in this study (e.g. CCRL1, CDHR3). We concluded that air liquid interface cultured human airway epithelial cells challenged with live HRV are a useful in vitro model for the study of rhinovirus induced asthma exacerbation, given that our findings are consistent with clinical data sets. Furthermore, our data suggest that abnormal airway epithelial structure and inflammatory signaling are important contributors to viral induced asthma exacerbation. Overall design: Differentiated air-liquid interface cultured human airway epithelial cell mRNA profiles from 6 asthmatic and 6 non-asthmatic donors after 24 hour treatment with either HRV or vehicle control were generated by deep sequencing, using Illumina HiSeq 2000.
Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.
No sample metadata fields
View SamplesOxidative stress is a hallmark of inflammation in infection or sterile tissue injury. We show that partially oxidized phospholipids of microvesicles (MVs) from plasma of patients with rheumatoid arthritis or cells exposed to oxidative stress induce activation of TLR4. MVs from healthy donors or reconstituted synthetic MVs can be converted to TLR4 agonists by limited oxidation, while prolonged oxidation abrogates the activity. Activation by MVs mimics the mechanism of TLR4 activation by LPS. However, LPS and MVs induce significantly different transcriptional response profile in mouse BMDMs with a strong inflammation-resolving component induced by the endogenous signals. MVs thus represent a ubiquitous endogenous danger signal released under the oxidative stress, which underlies the pervasive role of TLR4 signaling in inflammation.
Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in extracellular vesicles.
Sex
View SamplesYAP and TAZ play oncogenic roles in various organs, but the role of YAP/TAZ activation in gastric cancer in vivo has been understudied. We investigated whether and how YAP/TAZ initiates gastric tumorigenesis in vivo and its significance in human gastric cancer. We studied Lats1fl/fl;Lats2fl/fl;Lgr5-CreER mice, which have activated YAP/TAZ in pyloric stem cells. Gastric tissues were collected and analyzed by histopathology and immunostaining. To scrutinize the molecular mechanisms, we performed RNA sequencing in gastric tissue samples. Tissue microarray and public transcriptome data were analyzed to investigate the importance of YAP/TAZ in human gastric cancer. Overall design: Gastric pyloric tissue of Lats1fl/fl;Lats2fl/fl;Lgr5-CreER, or Lats1fl/fl;Lats2fl/fl mice that were 8 weeks after tamoxifen injection were collected in duplicates. RNAs were sequenced with Illumina NextSeq 500.
YAP/TAZ Initiates Gastric Tumorigenesis via Upregulation of MYC.
Specimen part, Cell line, Subject
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