Project description:A subset of medulloblastomas, the most common brain tumor in children, is hypothesized to originate from granule neuron precursors (GNPs) in which the sonic hedgehog (SHH) pathway is over-activated. MXD3, a basic helix-look-helix zipper transcription factor of the MAD family, has been reported to be upregulated during postnatal cerebellar development and to promote GNP proliferation and MYCN expression. Mxd3 is upregulated in mouse models of medulloblastoma as well as in human medulloblastomas. Therefore, we hypothesize that MXD3 plays a role in the cellular events that lead to medulloblastoma biogenesis. The purpose of this study was to identify changes in gene expression in response to MXD3. RNA from MXD3 stable cell lines compared to vector-only cell lines and to parental (DAOY) cell line.
Project description:Gene expression profiling of DAOY stable cell lines expressing a tamoxifen inducible MXD3. Data was normalized to a null version of MXD3 (unable to bind DNA). Goal of the study was to identify candidate genes regulated by MXD3.
Project description:This SuperSeries is composed of the following subset Series: GSE34050: ChIP-chip from DAOY cells stably expressing HA-MXD3 with anti-HA GSE34100: Expression profiling of MXD3 stable cell lines Refer to individual Series
Project description:A subset of medulloblastomas, the most common brain tumor in children, is hypothesized to originate from granule neuron precursors (GNPs) in which the sonic hedgehog (SHH) pathway is over-activated. MXD3, a basic helix-look-helix zipper transcription factor of the MAD family, has been reported to be upregulated during postnatal cerebellar development and to promote GNP proliferation and MYCN expression. Mxd3 is upregulated in mouse models of medulloblastoma as well as in human medulloblastomas. Therefore, we hypothesize that MXD3 plays a role in the cellular events that lead to medulloblastoma biogenesis. The purpose of this study was to identify MXD3 target genes. Stable cell line overexpressing HA tagged MXD3 immunoprecipitated with anti-HA; 2 biological replicates on 2 promoter arrays
Project description:A subset of medulloblastomas, the most common brain tumor in children, is hypothesized to originate from granule neuron precursors (GNPs) in which the sonic hedgehog (SHH) pathway is over-activated. MXD3, a basic helix-look-helix zipper transcription factor of the MAD family, has been reported to be upregulated during postnatal cerebellar development and to promote GNP proliferation and MYCN expression. Mxd3 is upregulated in mouse models of medulloblastoma as well as in human medulloblastomas. Therefore, we hypothesize that MXD3 plays a role in the cellular events that lead to medulloblastoma biogenesis. The purpose of this study was to identify MXD3 target genes.
Project description:A subset of medulloblastomas, the most common brain tumor in children, is hypothesized to originate from granule neuron precursors (GNPs) in which the sonic hedgehog (SHH) pathway is over-activated. MXD3, a basic helix-look-helix zipper transcription factor of the MAD family, has been reported to be upregulated during postnatal cerebellar development and to promote GNP proliferation and MYCN expression. Mxd3 is upregulated in mouse models of medulloblastoma as well as in human medulloblastomas. Therefore, we hypothesize that MXD3 plays a role in the cellular events that lead to medulloblastoma biogenesis. The purpose of this study was to identify changes in gene expression in response to MXD3.
Project description:Acute pancreatitis (AP) is a severe inflammatory disease where epithelial injury and dysregulated repair are central to pathogenesis, yet the underlying transcriptional mechanisms remain poorly understood. This study employed an integrated approach to identify and characterize the transcription factor MXD3 as a master regulator of AP progression. Using single-cell RNA sequencing in a cerulein-induced rat AP model, we delineated a pathogenic epithelial trajectory from ciliated through non-ciliated to a proliferative state, with MXD3 emerging as the most significantly upregulated transcription factor in the proliferative cluster. Subsequent validation in pancreatic ductal epithelial-specific MXD3 knockout rats revealed profound protection against AP, manifesting as reduced histological damage, diminished fibrosis, attenuated neutrophil infiltration (MPO+ cells), and decreased expression of pro-inflammatory cytokines (IL-6, TNF-a, IL-1b). Mechanistically, we demonstrated that MXD3 directly activates the Wnt/b-catenin pathway, as evidenced by increased non-phospho b-catenin, its nuclear accumulation, and transcriptional upregulation of canonical targets (c-Myc, Cyclin D1, Axin2). Furthermore, functional rescue experiments confirmed the pathway's necessity, wherein the b-catenin inhibitor ICG-001 substantially reversed MXD3-driven apoptosis, necrosis, and pro-inflammatory cytokine secretion (IL-1b, IL-6, MCP-1) in vitro. Our findings establish a novel MXD3-Wnt/b-catenin axis as a crucial mechanism governing epithelial pathology in AP, revealing MXD3 as a promising therapeutic target for this debilitating condition.
Project description:The goal of this study was to profile the total proteome and transcriptome of the established medulloblastoma cell lines, Daoy and UW228, using label-free nano-LC-MS/MS-based quantitative proteomics and high-throughput RNA sequencing (RNA-Seq), coupled with pathway analysis to identify differentially expressed genes, proteins and signaling pathways with potential as prognostic markers. A total of 14250 and 12870 transcripts were detected for Daoy and UW228, respectively. Proteomic profiling identified 2630 and 1235 proteins in Daoy and UW228, representing 18% and 10% of detected transcripts, respectively. Interestingly, Daoy proteome included >50% unique proteins, while almost 90% of proteins expressed by UW228 were commonly expressed in Daoy. Differential expression of a number of adhesion, cytoskeletal and signaling molecules were observed between the two cell lines. Upregulation of a number of proteins and enrichment of key signaling pathways, including WNT, Sonic hedgehog (SHH) and integrin signaling pathways, were uniquely observed in MB cell lines, in particular in Daoy.