Project description:Sonic hedgehog (Shh) signals via Gli transcription factors to stimulate proliferation of granule neuron precursor cells (GNPs) in the cerebellum. Deregulation of Shh target genes often results in unrestrained GNP proliferation and eventually medulloblastoma (MB), the most common pediatric brain malignancy. Gene expression profiling was coupled with transcription factor binding location analysis to determine the Gli1-controlled transcriptional regulatory networks in GNPs and medulloblastoma cells. We detected significant overlap, as well as differences, in the Gli1-controlled transcriptional regulatory networks in GNPs and MBs. We determined the presence of gene expression in each dataset. There were 9260 genes expressed in Gli1-FLAG GNPs and 9185 genes expressed in Gli1-FLAG;Ptc+/- tumors; 8691 of which are in common. The large overlap is consistent with the cellular origin of these tumors. When the genes detectably expressed were intersected with our binding data, there were only 132 putative Gli1 target genes shared by both cell populations. Due to the heightened activation of the Hh pathway in tumors relative to GNPs, we further deduced direct Gli1 target genes exclusive to tumors by determining significantly induced genes in tumors versus in Ptc+/- GNPs. We identified at least 116 tumor-specific Gli1 target genes. These data suggest that tumor formation is accompanied by a tremendous change in the battery of Gli target genes. Presence of gene expression was determined for all samples: Gli1-FLAG-expressing GNPs, Ptc+/- GNPs, and Gli1-FLAG;Ptc+/-medulloblastomas. These datasets were intersected with chIP-chip data to determine potential direct Gli1 target genes. Differential gene expression was determined by comparing expression profiles from medulloblastoma tumors to those from Ptc+/- GNPs.
Project description:Sonic hedgehog (Shh) signals via Gli transcription factors to stimulate proliferation of granule neuron precursor cells (GNPs) in the cerebellum. Deregulation of Shh target genes often results in unrestrained GNP proliferation and eventually medulloblastoma (MB), the most common pediatric brain malignancy. Gene expression profiling was coupled with transcription factor binding location analysis to determine the Gli1-controlled transcriptional regulatory networks in GNPs and medulloblastoma cells. We detected significant overlap, as well as differences, in the Gli1-controlled transcriptional regulatory networks in GNPs and MBs. We determined the presence of gene expression in each dataset. There were 9260 genes expressed in Gli1-FLAG GNPs and 9185 genes expressed in Gli1-FLAG;Ptc+/- tumors; 8691 of which are in common. The large overlap is consistent with the cellular origin of these tumors. When the genes detectably expressed were intersected with our binding data, there were only 132 putative Gli1 target genes shared by both cell populations. Due to the heightened activation of the Hh pathway in tumors relative to GNPs, we further deduced direct Gli1 target genes exclusive to tumors by determining significantly induced genes in tumors versus in Ptc+/- GNPs. We identified at least 116 tumor-specific Gli1 target genes. These data suggest that tumor formation is accompanied by a tremendous change in the battery of Gli target genes.
Project description:The data includes a transcriptome analysis of K562 cell lines in which the gene N-glycanase 1 (NGLY1) was mutated in exon 1 and/or exon 3 to include loss of function mutations as described in Mueller and Jakob et al, 2020. The data were used in conjunction with whole proteome MS/MS experiments to show a gene expression profile consistent with NGLY1 deficiency, a human disease. The experiments demonstrate the wide ranging effect of the loss of NGLY1 on a cellular system.
Project description:The aim of this project is to promote the breath volatile marker concept for colorectal cancer (CRC) screening by advancing developing the application of a novel hybrid analyzer for the purpose.
The hybrid analyzer concept is expected to benefit of combining metal-oxide (MOX) and infrared spectrum (IR) sensor acquired data. The current study will be the first globally to address this concept in CRC detection. In addition, traditional methods, in particular, gas chromatography coupled to mass spectrometry (GC-MS) will be used to address the biological relevance of the VOCs emission from cancer tissue and will assist in further advances of the hybrid-sensing approach.
Project description:This study explores the role of Ezh2 in delaying the activation of differentiation genes during the development of cerebellar granule neurons (GNPs) and in SHH subtype medulloblastoma. To investigate the epigenetic landscape, we performed chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) on GNPs and medulloblastoma cells derived from Ptch1 heterozygous mice. We profiled histone modifications and key regulatory proteins, including H3K27me3, H3K27ac, H3K36me3, H3K4me3, H3K4me1, H2Aubi119, Ring1b, and Pol2S5. Additionally, we conducted ATAC-seq to assess chromatin accessibility and MIRA-seq to study DNA methylation. This dataset aims to compare the epigenetic state of normal granule neuron progenitors with that of medulloblastoma cells, providing insight into how epigenetic mechanisms contribute to neuronal differentiation. We found that the inhibition of Ezh2-mediated H3K27 methylation represses differentiation in both GNPs and medulloblastoma cells.
Project description:This study explores the role of Ezh2 in delaying the activation of differentiation genes during the development of cerebellar granule neurons (GNPs) and in SHH subtype medulloblastoma. To investigate the epigenetic landscape, we performed chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) on GNPs and medulloblastoma cells derived from Ptch1 heterozygous mice. We profiled histone modifications and key regulatory proteins, including H3K27me3, H3K27ac, H3K36me3, H3K4me3, H3K4me1, H2Aubi119, Ring1b, and Pol2S5. Additionally, we conducted ATAC-seq to assess chromatin accessibility and MIRA-seq to study DNA methylation. This dataset aims to compare the epigenetic state of normal granule neuron progenitors with that of medulloblastoma cells, providing insight into how epigenetic mechanisms contribute to neuronal differentiation. We found that the inhibition of Ezh2-mediated H3K27 methylation represses differentiation in both GNPs and medulloblastoma cells.