This study revealed pathogenic role of pre-BCR-independent SYK activation in high-risk B-ALL.
Therapeutic potential of spleen tyrosine kinase inhibition for treating high-risk precursor B cell acute lymphoblastic leukemia.
Specimen part
View SamplesMicrosatellite expansions often occur in non-coding regions of the genome. In this study, we test their effect on host transcript RNA processing. Overall design: RNA-seq on affected tissues and peripheral blood from control and affected patients.
Intron retention induced by microsatellite expansions as a disease biomarker.
Specimen part, Disease, Subject
View SamplesWe sequenced mRNA from Left Ventricles of Streptozotocin induced Type I diabetic mouse hearts or mock treated controls at 4 weeks post-treatment in order to assess alternative splicing changes. Overall design: Heart mRNA profiles of Control and Diabetic (STZ:T1D) mice were generated by deep sequencing using Illumina HiSeq 1000.
Dysregulation of RBFOX2 Is an Early Event in Cardiac Pathogenesis of Diabetes.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesEts1-/- mice have an increase in B cell differentiation to plasma cells and increased serum immunoglobulin levels. The genes in B cells that are transcriptionally regulated by Ets1 and help regulate B cell differentiation are largely unknown. Here, we identify Ets1-regulated target genes in B cells using ChIP-seq and RNA-seq analysis. We found that Ets1 targets genes associated with immune response, mature B cell differentiation and regulation of B cell activation. Overall design: Quiescent follicular B cells were sorted from the spleens of wild-type and Ets1-/- mice using the following markers B220+ CD23-high CD21-low CD80-negative IgA-negative IgE-negative IgG1-negative IgG2a-negative IgG2b-negative IgG3-negative. Total RNA was prepared from sorted cells and subjected to RNA-sequencing.
Genome-Wide Identification of Target Genes for the Key B Cell Transcription Factor <i>Ets1</i>.
Specimen part, Cell line, Subject
View SamplesOverall study: Identification of PDGF-dependent patterns of gene expression in U87 glioblastoma cells.
Autocrine platelet-derived growth factor-dependent gene expression in glioblastoma cells is mediated largely by activation of the transcription factor sterol regulatory element binding protein and is associated with altered genotype and patient survival in human brain tumors.
No sample metadata fields
View SamplesLYVE-1-positive macrophages were observed to be closely spatially associated with the developing lymphatic vasculature. The role of this population of macrophages in the embryo is uncharacterised.
Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation.
No sample metadata fields
View SamplesThe Ets family transcription factor PU.1 is essential for the development and maintenance of several hematopoietic lineages. In the thymus, PU.1 is expressed only in the early ETP/DN1, DN2a and DN2b stages of development. While PU.1 deletion in multipotent precursors leads to a complete block in T-cell development its function in the intrathymic stages in which it is expressed remains undetermined. The goal of this expression profiling study was to determine if PU.1 regulates the expression of T-lineage genes during the early stages of development. To do this, we generated the PU.1-Eng construct which expresses a fusion protein containing the DNA binding ETS domain of PU.1 (aas 159-260) fused to the obligate repressor domain (aas 1-298) of the Drosophila engrailed protein. The PU.1-ETS construct only expresses the ETS domain of PU.1 (aas 159-260) and serves as a control. Fetal liver precursors were isolated from e14.5 embryos and co-cultured with OP9-DL1 cells in the presence of IL-7 and Flt3L (5 ng/ml each) for 4 days to obtain FLDN1, DN2a and DN2b cells. These were infected with vector only, PU.1-ETS and the PU.1-Eng constructs and DN2 cells were sorted after 20 hours of infection. Total RNA was isolated from these cells and polyA+ fraction was used to prepare libraries for high throughput sequencing. Libraries prepared from 2 independent sets of samples were subjected to non-strand specific single-end sequencing. Overall design: Two sets of samples generated from fetal liver precursor derived DN2 cells expressing PU.1-ETS and PU.1-Eng constructs were used for expression profiling. The LZRS retroviral vector, without any insert, was used to generate the vector control dataset.
Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1.
No sample metadata fields
View SamplesPlasma cell differentiation involves coordinated changes in gene expression and functional properties of B cells. Here, we study the role of Mzb1, a Grp94 co-chaperone that is expressed in marginal zone (MZ) B cells and during the terminal differentiation of B cells to antibody-secreting cells (ASCs). By analyzing Mzb1 -/- Prdm1 +/gfp mice, we find that Mzb1 is specifically required for the differentiation and function of ASCs in a T cell-independent immune response. We find that Mzb1-deficiency mimics, in part, the phenotype of Blimp1 deficiency, including the impaired secretion of IgM and the deregulation of Blimp1 target genes. In addition, we find that Mzb1 -/- plasmablasts show a reduced activation of b1 integrin, which contributes to the impaired plasmablast differentiation and migration of ASCs to the bone marrow. Thus, Mzb1 function is required for multiple aspects of plasma cell differentiation. Overall design: Splenic B cells were purified from Mzb1 +/+ Prdm1 +/gfp and Mzb1 -/- Prdm1 +/gfp mice using anti-B220 magnetic beads and cultured in the presence of 25ug/ml LPS. After 4 days, undifferentiated CD138 - Blimp - B cell blasts (Activated B Cells), CD138 - Blimp + (Pre-PB cells), and CD138 + Blimp + (PB cells) were isolated with FACSAria (Becton Dickinson) sort.
Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and β1-integrin function.
Specimen part, Cell line, Subject
View SamplesBy comparing to common tumor cells, genes were differencially expressed in pseudopalisading cells in human glioblastoma
Histology-based expression profiling yields novel prognostic markers in human glioblastoma.
No sample metadata fields
View SamplesMEG3 (Maternally Expressed Gene 3) is a non-coding RNA that is highly expressed in the normal human brain and pituitary. Expression of MEG3 is lost in gonadotroph-derived clinically non-functioning pituitary adenomas. Meg3 knock-out mice were generated to identify targets and potential functions of this gene in embryonic development and tumorigenesis. Gene expression profiles were compared in the brains of Meg3-null embryos and wild-type litter-mate controls using microarray analysis. Microarray data were analyzed with GeneSifter which uses Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) classifications to identify signaling cascades and functional categories of interest within the data set. Differences were found in signaling pathways and ontologies related to angiogenesis between wild-type and knock-out embryos. Quantitative RT-PCR and histological staining showed increased expression of some VEGF pathway genes and increased cortical microvessel density in the knock-out embryos. These results are consistent with reported increases in VEGF signaling observed in human clinically non-functioning pituitary adenomas. In conclusion, Meg3 may play an important role in control of vascularization in the brain and may function as a tumor suppressor by preventing angiogenesis.
Increased expression of angiogenic genes in the brains of mouse meg3-null embryos.
Specimen part
View Samples