Fumarylacetoacetate hydrolase (Fah), the last enzyme of the tyrosine degradation pathway, is specifically expressed in hepatocytes in the liver. Loss of Fah leads to liver failure in mice within 6-8 weeks. This can be prevented by blocking tyrosine degradation upstream of Fah with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC). Here, we investigate the impact of p21 on global gene expression in Fah deficiency.
Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis.
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View SamplesGeneration of human fibroblast-derived hepatocytes capable of extensive proliferation, as evidenced by significant liver repopulation of mice. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs, but shortcut reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) stage from which endoderm progenitor cells (iMPC-EPCs) and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps were able to engraft and proliferate, and acquired levels of hepatocyte function similar to adult hepatocytes.
Mouse liver repopulation with hepatocytes generated from human fibroblasts.
Specimen part
View SamplesWe analyzed gene expression profiles of IL-18 generated murine NK cells in comparison to unstimulated, freshly isolated splenic NK cells.
Immunoregulatory natural killer cells suppress autoimmunity by down-regulating antigen-specific CD8+ T cells in mice.
Specimen part, Treatment
View SamplesAnaplastic large cell lymphoma (ALCL) is a main type of T cell lymphomas and comprises three distinct entities: systemic ALK+, systemic ALK- and cutaneous ALK- ALCL. Little is known about their pathogenesis and their cellular origin, and morphological and immunophenotypical overlap exists between ALK- ALCL and classical Hodgkin lymphoma (cHL). We conducted gene expression profiling of microdissected lymphoma cells of ALK+ and ALK- systemic ALCL, cutaneous ALCL and cHL, and of eight subsets of normal T and NK cells. The analysis supports a derivation of ALCL from activated T cells, but the lymphoma cells acquired a gene expression pattern hampering an assignment to a CD4+, CD8+ or CD30+ T cell origin. Indeed, ALCL display a general down-modulation of T cell characteristic molecules. All ALCL types show significant expression of NFB target genes and upregulation of genes involved in oncogenesis (e.g. EZH2). Surprisingly few genes are differentially expressed between systemic and cutaneous ALK- ALCL despite their different clinical behaviour, and between ALK- ALCL and cHL despite their different cellular origin. ALK+ ALCL are characterized by expression of genes regulated by pathways constitutively activated by ALK. This study provides multiple novel insights into the molecular biology and pathogenesis of ALCL.
Gene expression profiling of isolated tumour cells from anaplastic large cell lymphomas: insights into its cellular origin, pathogenesis and relation to Hodgkin lymphoma.
Specimen part
View SamplesThis experiment aims to identify the biological pathways and diseases associated with the cytokine Interleukin 13 (IL-13) using gene expression measured in peripheral blood mononuclear cells (PBMCs). Overall design: The experiment comprised of samples obtained from 3 healthy donors. The expression profiles of in vitro IL-13 stimulation were generated using RNA-seq technology for 3 PBMC samples at 24 hours. The transcriptional profiles of PBMCs without IL-13 stimulation were also generated to be used as controls. An IL-13R-alpha antagonist (Redpath et al. Biochemical Journal, 2013) was introduced into IL-13 stimulated PBMCs and the gene expression levels after 24h were profiled to examine the neutralization of IL-13 signaling by the antagonist.
Combining multiple tools outperforms individual methods in gene set enrichment analyses.
No sample metadata fields
View SamplesWe performed mRNA-seq of a PRKACA-mutant adrenal tumor and demonstrated that the mutation is expressed at the mRNA level. Overall design: Total RNA obtained from a cortisol-producing adrenal tumor with a PRKACA p.Leu206Arg mutation.
Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors.
No sample metadata fields
View SamplesDatabase of gene expression in different haematopoietic cell types at haemosphere.org Overall design: Comparison of gene expression in different haematopoietic cell types
Haemopedia RNA-seq: a database of gene expression during haematopoiesis in mice and humans.
Specimen part, Subject
View SamplesG-CSF is a hemopoietic growth factor that has a role in steady state granulopoiesis, as well as in mature neutrophil activation and function. We developed a neutralizing monoclonal antibody to the murine G-CSF receptor (G-CSFR), which antagonizes binding of murine G-CSF and inhibits G-CSFR signalling. Anti-G-CSFR rapidly halts the progression of established disease in collagen antibody-induced arthritis (CAbIA). Neutrophil accumulation in joints is inhibited, without rendering animals neutropenic, suggesting an effect on homing to inflammatory sites. Neutrophils in the blood and arthritic joints of anti-G-CSFR treated mice show alterations in cell adhesion receptors, while anti-G-CSFR suppresses local production of proinflammatory cytokines and chemokines known to drive tissue damage. Our aim in this study was to use differential gene expression analysis of joint and blood neutrophils to more thoroughly understand the effect of G-CSFR blockade on the inflammatory response following anti-G-CSFR therapy in CAbIA.
Therapeutic Targeting of the G-CSF Receptor Reduces Neutrophil Trafficking and Joint Inflammation in Antibody-Mediated Inflammatory Arthritis.
Sex, Specimen part, Disease, Disease stage, Treatment
View SamplesA systematic survey of the transcriptional status of individual segments of the developing chick hindbrain (r1-5) and the adjacent region of the embryonic midbrain (m) during the HH11 stage of chick development
Transcriptomic analysis of midbrain and individual hindbrain rhombomeres in the chick embryo.
Specimen part
View SamplesThe sarcosine oxidase locus is controlled by GbdR and SouR independently induced by glycine betaine and sarcosine, respectively. The goal of this study was to identify the members of the SouR regulon. Therefore, the comparison strains were a gbdR mutant and a gbdRsouR double mutant.
Sarcosine Catabolism in Pseudomonas aeruginosa Is Transcriptionally Regulated by SouR.
Treatment
View Samples