Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA273609 | ENA |
REPOSITORIES: ENA
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Project description:The cytokine TSLP stimulates in vitro proliferation of human fetal B cell progenitors. Genetic alterations that cause overexpression of the TSLP receptor component, CRLF2, lead to B cell acute lymphoblastic leukemia (CRLF2 B-ALL) with poor outcome. The in vivo role of TSLP in normal human B cell development and its contribution to CRLF2 B-ALL are unknown. In classic xenograft models CRLF2-mediated signaling is unlikely to be activated by mouse TSLP, based on data from engineered cellular models. Here, we show that mouse TSLP does not induce activation of the CRLF-2 downstream pathways (JAK/STAT and AKT/mTOR) that are induced by human TSLP (hTSLP) in CRLF2 B-ALL cells. Based on this, we developed a novel human-mouse xenograft model system comprised of mice that produce hTSLP (+T mice) to activate human CRLF2-mediated signaling and mice that lack hTSLP (–T mice). Normal serum levels of hTSLP were achieved in +T mice, while hTSLP was undetectable in –T mice. hTSLP produced by stroma induced JAK/STAT and AKT/mTOR pathway activation and showed functional in vivo effects on normal human B cell progenitors and primary CRLF2 B-ALL cells. Whole genome microarray of primary CRLF2 B-ALL showed an induction of mTOR regulated gene expression and preservation of TSLP responsiveness in cells expanded in +T mice as compared to –T mice.
2016-05-03 | GSE65274 | GEO
Project description:Xenograft models represent an excellent method for expanding primary leukemias, but their ability to preserve the gene expression profile of the parent leukemia may also depend on providing microenvironmental factors that are not cross-reactive between human and mouse. Here we focused on leukemias with a CRLF2 mutation, and the ability of human TSLP to stimulate these cells. Three different classes of samples were analyzed. 1) The primary leukemia sample without any culture or treatment 2) Xenograft samples (2) of the primary leukemia that were exposed to TSLP in vivo for 2 weeks, 9 weeks post-engraftment and 3) Xenograft samples (2) of the primary leukemia that were NOT exposed to TSLP in vivo for 2 weeks, 9 weeks post-engraftment.
2015-12-31 | E-GEOD-74339 | biostudies-arrayexpress
Project description:Xenograft models represent an excellent method for expanding primary leukemias, but their ability to preserve the gene expression profile of the parent leukemia may also depend on providing microenvironmental factors that are not cross-reactive between human and mouse. Here we focused on leukemias with a CRLF2 mutation, and the ability of human TSLP to stimulate these cells.
2015-12-31 | GSE74339 | GEO
Project description:The inflammatory response is associated with cardiac repair and ventricular remodeling after myocardial infarction (MI). The key inflammation regulatory factor thymic stromal lymphopoietin (TSLP) plays a critical role in various diseases. However, its role in cardiac repair after MI remains uncertain. In this study, we elucidated the biological function and mechanism of action of TSLP in cardiac repair and ventricular remodeling following MI. Wild-type and TSLP receptor (TSLPR)-knockout (Crlf2-/-) mice underwent MI induction via ligation of the left descending artery. TSLP expression was upregulated in the infarcted heart, with a peak observed on day 7 post-MI. TSLP expression was enriched in the cardiomyocytes of infarcted hearts, with the highest expression observed in dendritic cells. Crlf2-/- mice exhibited significantly reduced survival and worsened cardiac function, increased interstitial fibrosis and cardiomyocyte cross-sectional area, and reduced CD31+ staining, with no change in the proportion of apoptotic cardiomyocytes within the border zone. Mechanistically, a reduction in regulatory T cells and more innate immune cells and their subsets were observed in the infarcted hearts of Crlf2-/- mice, accompanied by a systemic reduction in T cell activation and proliferation. Simultaneously, RNA sequencing analysis of the infarcted hearts revealed significant downregulation of genes in Crlf2-/- mice. Our findings indicate that TSLP plays a pivotal role in regulating T cell responses, specifically T regulatory cells, thus promoting cardiac repair, which may provide a potential novel therapeutic approach for managing heart failure after MI.
2024-09-21 | GSE265931 | GEO
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:TSLP effects on primary human blood dendritic cells
| PRJNA254794 | ENA
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs. One-condition experment, gene expression of 3A6
2010-09-25 | E-GEOD-24338 | biostudies-arrayexpress