We have examined the biological effect of EWS/ETS in human MPCs using UET-13 cells that are obtained by prolonging the lifespan of human bone marrow stromal cells using the retroviral transgenes hTERT and E7. By exploiting tetracycline-inducible systems for expressing EWS/ETS (EWS/FLI1 and EWS/ERG), we investigated candidates for genes whose expression is regulated by EWS/ETS in human MPCs.
Inducible expression of chimeric EWS/ETS proteins confers Ewing's family tumor-like phenotypes to human mesenchymal progenitor cells.
No sample metadata fields
View SamplesFor identification of candidate genes that is specifically expressed in Ewing family tumor (EFT) cells, we performed DNA microarray-based global expression profiling using Affymetrix Human Genome U133 Plus 2.0 Array and analyxed expression profiles from EFT cell lines (7 lines), neuroblastoma (NB) cell lines (3 lines), a Rhabdomyosarcoma (RMS) cell line, and a human immortalized mesenchymal progenitor cells UET-13 cells.
Inducible expression of chimeric EWS/ETS proteins confers Ewing's family tumor-like phenotypes to human mesenchymal progenitor cells.
No sample metadata fields
View SamplesPOU5F1 (more commonly known as Oct-4/3) is one of the stem cell markers and affects direction of differentiation in embryonic stem cells. To investigate whether cells of mesenchymal origin acquire embryonic phenotype, we generated a human cell line of mesodermal origin with overexpression of the chimeric POU5F1 gene with physiological co-activator EWS, which is driven by the potent EWS promoter by translocation. The cell line termed Pooh (POU5F1/Oct-4/3 overexpressing human) cells expressed embryonic stem cell genes such as Nanog and also non-translocated POU5F1, lost mesenchymal phenotypes, and exhibited embryonal stem cell-like alveolar structure when implanted into the subcutaneous tissue of immunodeficient mice. Hierarchical analysis by microchip analysis and cell surface analysis revealed that Pooh cells are subcategorized into the group of human embryonic stem cells and embryonal carcinoma cells. These results imply that cells of mesenchymal origin can partially be traced back to cells to embryonic phenotype by the POU5F1 gene in collaboration with the potent cis-regulatory element and the fused co-activator.
Mesenchymal to embryonic incomplete transition of human cells by chimeric OCT4/3 (POU5F1) with physiological co-activator EWS.
No sample metadata fields
View SamplesPhiladelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a distinct subtype of B-ALL with a poor prognosis. Rearrangement of LYN is a recurrent genetic abnormality in Ph-like ALL, but functional analysis of LYN-related fusion genes identified in ALL has not been reported. In this study, we performed functional analysis of the NCOR1-LYN fusion gene identified in a pediatric Ph-like ALL patient to establish its potential for molecular targeted therapy. Retroviral transduction of interleukin (IL)-3-dependent Ba/F3 cells with NCOR1-LYN enabled IL-3-independent proliferation, with constitutive phosphorylation of the tyrosine residues of the LYN kinase domain in the fusion protein. Replacing tyrosine residues with phenylalanine in the LYN kinase domain abolished IL-3 independence. Tyrosine kinase inhibitor dasatinib killed Ba/F3 cells expressing NCOR1-LYN in vitro accompanied by dephosphorylation of the tyrosine residues of the LYN kinase domain in the fusion protein.
Leukemic cells expressing NCOR1-LYN are sensitive to dasatinib in vivo in a patient-derived xenograft mouse model.
Cell line
View SamplesB-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous disease that can be subdivided according to primary recurrent genetic abnormalities that are strongly associated with characteristic biological and clinical features. The detection of these abnormalities can facilitate diagnosis, risk stratification, and targeted therapy.
ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype.
Specimen part
View SamplesWe used an IL4-capture assay followed by FACS sorting, to isolate IL4-secreting TFH cells from a human tonsil and compared their transcriptomic profiles with CXCR5hi PD1hi IL4-negative tonsillar TFH cells and IL4-producing CXCR5neg non-TFH cells (TH2 cells). Our studies validate the notion of functionally distinct TFH subsets and identify genes that are specifically expressed in and define the human IL-4 secreting TFH cell subset. Overall design: T follicular helper cell subset mRNA profiles from human tonsils were generated by deep sequencing. Naive CD4 T cells, IL4-producing nonTFH CD4 T cells (i.e. TH2), and IL4-producing TFH cells and PD1hi TFH cells were analyzed. DOI: 10.26508/lsa.201800050
The expansion in lymphoid organs of IL-4<sup>+</sup> BATF<sup>+</sup> T follicular helper cells is linked to IgG4 class switching in vivo.
Specimen part, Subject
View SamplesWe found a new spontaneous mutant mouse, laggard, characterized by general weakness in movements and retardation in growth.
Kif14 mutation causes severe brain malformation and hypomyelination.
Specimen part
View SamplesWaldenstom macroglobulinemia (WM) with 6q del is still unknown. In the present study, we analyzed gene expression signiture of WM with 6q del.
Gene Expression Profile Signature of Aggressive Waldenström Macroglobulinemia with Chromosome 6q Deletion.
Specimen part, Disease
View SamplesIntratracheal transfer of isolated lung fibroblasts in bleomycin-induced lung fibrosis recapitulates the activation process of lung fibroblasts after epithelial injury. In order to investigate gene expression signatures of transferred fibroblasts, we purified transferred fibroblasts 2, 4, and 7 days after the transfer and performed transcriptome analysis. We also isolated Acta2 high and low cells by using Acta2-mKO1 reporter mice 4 days after the transfer. Overall design: Lung fibroblasts were isolated from untreated Col-GFP mice after tissue dissociation and negative selection for lineage markers. Isolated lung fibroblasts were intratracheally transferred into wild type mice, which received intratracheal bleomycin treatment 7 days before the transfer. Col-GFP+ cells were purified from the host lungs by FACS sorting on 2, 4, and 7 days after the transfer. Acta2 high and low cells were prepared by transferring lung fibroblasts from Acta2-mKO1 reporter mice. mRNA was isolated from sorted cells, and gene expression profiles were acquired by next generation sequencing.
Gli signaling pathway modulates fibroblast activation and facilitates scar formation in pulmonary fibrosis.
Cell line, Subject
View SamplesThe spontaneous pulmonary metastasis model of human uterine sarcoma was established using GFP-expressed MES-SA cells. Several sublines with different metastatic potentials were generated by in vivo passaging.
Establishment and characterization of a novel orthotopic mouse model for human uterine sarcoma with different metastatic potentials.
Sex, Specimen part
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