Background: The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development and susceptibility to schizophrenia and bipolar disorder.
Identification of the BRD1 interaction network and its impact on mental disorder risk.
Cell line
View SamplesCTLA-4 is thought to inhibit effector T cells both intrinsically, by competing with CD28 for B7 ligands, and extrinsically, through the action of regulatory T cells. We studied in vivo responses of normal and CTLA-4-deficient antigen-specific murine effector CD4+ T cells. In order to do these studies in a physiological model of immunity to foreign antigen, we transferred small numbers of congenically marked RAG2-deficient 5C.C7 T cells with either a normal or knockout allele of CTLA-4 into normal syngeneic B10.A recipient mice. The T cells were then activated by immunization with MCC peptide and LPS. To look for transcriptional signatures of negative regulation of T cell responses by CTLA-4, we used microarray analysis to compare transcripts in wild type and CTLA-4 KO 5C.C7 T cells four days after immunization. This is the first instance in which differences are observed in extent of accumulation of wild type and CTLA-4 KO 5C.C7 T cells.
Cutting edge: CTLA-4 on effector T cells inhibits in trans.
Specimen part
View SamplesA LHX4 transgenic reporter line with high specificity for developing mouse cone photoreceptors was identified and used to purify early stage cone photoreceptors for profiling by single cell RNA sequencing. Overall design: Collection of FACS-sorted LHX4::GFP+ E14.5 early cones and LHX4::GFP- retinal cells for further analysis.
Identification of Genes With Enriched Expression in Early Developing Mouse Cone Photoreceptors.
Specimen part, Cell line, Subject
View SamplesAnalysis of knockdown of SDHD with or without knockdown of CDKN1C or SLC22A18 at gene expression level.
Parent-of-origin tumourigenesis is mediated by an essential imprinted modifier in SDHD-linked paragangliomas: SLC22A18 and CDKN1C are candidate tumour modifiers.
Specimen part, Cell line
View SamplesGene expression profiling with microarrays was used to identify genes differentially expressed in the lungs of B6 and BALB CF mice compared to non-CF littermates
Strain-dependent pulmonary gene expression profiles of a cystic fibrosis mouse model.
No sample metadata fields
View SamplesCystic fibrosis transmembrane conductance regulator (Cftr) knockout mice present the clinical features of low body weight and intestinal disease permitting an assessment of the interrelatedness of these phenotypes in a controlled environment. To identify intestinal alterations which affect body weight in CF mice the histological phenotypes of crypt-villus axis height, goblet cell hyperplasia, and mast cell infiltrate were measured, cardiac blood samples assessed, and gene expression profiling of the ileum was completed for 12 week old (C57BL/6xBALB) F2 Cftrtm1UNC and non-CF mice presenting a range of body weight. Crypt-villus axis height decreased with increasing weight in CF, but not control, mice. Goblet cell hyperplasia and mast cell infiltration in the submucosa and muscularis externa layers of the CF intestine, were identified to be independent of bodyweight. Blood triglyceride levels were found to be significantly lower in CF mice than control mice (p = 3.02 x 10-5) but were not dependent on CF mouse body weight. By expression profiling, genes of DNA replication and lipid metabolism were among those altered in CF mice relative to non-CF controls; and no differences in gene expression were measured between samples from CF mice in the 25th and 75th percentile for weight. This study indicates that the absence of Cftr leads to altered morphology in the CF intestine the extent of which is correlated with body weight in CF mice while CF related changes in blood triglyceride levels and in the intestinal gene expression profile were not dependent on body weight in this model.
Intestinal phenotype of variable-weight cystic fibrosis knockout mice.
Sex
View SamplesCure rates for patients with acute myeloid leukemia (AML) remain low despite ever-increasing dose intensity of cytotoxic therapy. In an effort to identify novel approaches to AML therapy, we recently reported a new method of chemical screening based on the modulation of a gene expression signature of interest. We applied this approach to the discovery of AML-differentiation-promoting compounds. Among the compounds inducing neutrophilic differentiation was DAPH1 (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here we report that the Food and Drug Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphologic assessment, nitro-blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene expression, and inhibition of proliferation at clinically achievable doses. Importantly, EGFR expression was not detected in AML cells, indicating that gefitinib functions through a previously unrecognized EGFR-independent mechanism. These studies indicate that clinical trials testing the efficacy of gefitinib in patients with AML are warranted.
Gefitinib induces myeloid differentiation of acute myeloid leukemia.
Disease, Disease stage, Cell line
View SamplesVarious mesenchymal cell types have been identified as critical components of the hematopoietic stem/progenitor cell (HSPC) niche. Although several groups have described the generation of mesenchyme from human pluripotent stem cells (hPSC), the capacity of such cells to support hematopoiesis has not been reported. Here we have demonstrated that distinct mesenchymal subpopulations co-emerge from mesoderm during hPSC differentiation. Despite co-expression of common mesenchymal markers (CD73, CD105, CD90, PDGFRß), a subset of cells defined as CD146++CD140alow supported functional HSPC ex vivo while CD146-CD140a+ cells drove differentiation. The CD146++ subset expressed genes associated with the HSPC niche and high levels of the Wnt inhibitors. HSPC support was contact-dependent and was mediated in part through JAG1 expression. Molecular profiling revealed remarkable transcriptional similarity between hPSC-derived CD146++ and primary human CD146++ perivascular cells. The derivation of diverse pools of mesenchymal populations from hPSC opens potential avenues to model their developmental and functional differences and to improve cell-based therapeutics from hPSC. Overall design: Our goal was to analyze and compare transcriptome of human pluripoten stem cell-derived mesenchyme (CD146++ and CD146-) with primary human lipoaspirate tissue-derived pericyte (CD146+) and CD146- mesenchymal populations.
Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation.
Specimen part, Cell line
View SamplesWe used microarrays to determine how the quality and quantity of peptide-MHC impact TCR-induced gene expression in vivo.
Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses.
No sample metadata fields
View Samples