Using human induced pluripotent stem cell-derived oligodendrocytes to explore cellular phenotypes associated with t(1;11) translocation.
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ABSTRACT:
PROVIDER: EGAS00001004595 | EGA |
REPOSITORIES: EGA
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Project description:Despite modern approaches to the diagnosis and treatment of acute bowel obstruction (ABO), postoperative mortality ranges from 5 to 32%, and complications occur up 23% of cases. One of the formidable infectious and inflammatory complications of ABO is sepsis. The main component of the development of sepsis in ABO is bacterial translocation (BT). BT is the migration of intestinal bacteria or their products through the intestinal mucosa into the mesenteric lymph nodes and further into normally sterile tissues and organs.
Today there are several methods for detecting BT:
1. direct method - the detection of 16s rRNA (ribosomal ribonucleic acid) in mesenteric lymph nodes (MLN);
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Project description:Chromosome translocation plays a crucial role in the development of tumors, but its underlying biological mechanisms, especially in human cells, remain poorly understood. In this study, we aimed to shed light on the mechanisms governing chromosome translocation in K562 cells. To investigate this, we initiated the process by inducing two double-strand breaks (DSBs) using Cas9 sgRNA and subsequently quantified the frequency of chromosome translocation events. Furthermore, we explored the influence of several compounds by introducing them alongside the DSBs, allowing us to assess their impact on chromosome translocation. Our research unveiled the identification of two noteworthy compounds, HDAC inhibitors and HSP90 inhibitors, which were found to significantly enhance the occurrence of chromosome translocation. These findings contribute to a deeper understanding of the molecular processes involved in tumorigenesis and provide potential targets for future therapeutic interventions.
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Project description:Transcriptome of JAZF1-SUZ12 translocation
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Project description:Renal Cell Carcinoma (RCC) associated with Xp11.2 translocation (TFE3-RCC) has been recently defined as a distinct subset of RCC. The Xp11 translocations involve the TFE3 transcription factor and produce chimeric TFE3 proteins retaining the basic helix-loop-helix leucine zipper structure for dimerization. To facilitate the development of molecular-based diagnostic tools and targeted therapies for TFE3-RCC, we generated a translocation RCC mouse model and performed DNA microarray analysis.
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Project description:Three Ten-Eleven Translocation (Tet) enzymes are epigenetic regulators of gene expression that promote 5-hydroxymethylcytosine (5hmC) modification of genes. Here, we show that the loss of Tet2 can induce depression-like phenotypes in mice. Paradoxically, using the paradigms of chronic stress, such as chronic mild stress (CMS) and chronic social defeat stress (CSDS), we found that depressive behaviors were associated with increased Tet2 expression but decreased global 5hmC level in hippocampus. We examined the genome-wide 5hmC profile in the hippocampus of Tet2 knockout mice and identified 651 dynamically hydroxymethylated regions, 31 of which overlapped with known depression-associated loci. We further showed that chronic stress could induce the abnormal nuclear translocation of Tet2 protein from cytosol. Through Tet2 immunoprecipitation and mass spectrum analyses, we identified a cellular trafficking protein, Abelson helper integration site-1 (Ahi1), which could interact with Tet2 protein. Ahi1 knockout or knockdown caused the accumulation of Tet2 in cytosol. The reduction of Ahi1 protein under chronic stress explained the abnormal Ahi1-dependent nuclear translocation of Tet2. These findings together provide the evidence for a critical role of modulating Tet2 nuclear translocation in regulating stress response.
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Project description:DNA-PKcs is a crucial component of the non-homologous end joining (NHEJ) repair machinery. To investigate its function in human cell lines, we conducted a study using K562 and HEK293T cell lines. We introduced twinned DNA double-strand breaks (DSBs) or genome-wide DSBs into these cell lines via nucleofection and transfection, respectively. Subsequently, we employed high-throughput genome translocation sequencing (HTGTS) to capture the translocation events (i.e., ligation between "prey(s)" and "bait") and the rejoining events (i.e., direct repair within the "bait" locus) under different conditions, including with or without DNA-PKcs inhibition or deletion. We quantified the number of translocation events by normalizing them to the number of rejoining events, denoted as TL. Interestingly, DNA-PKcs inhibition led to an increase in TL, indicating a higher frequency of translocations. However, it is important to note that chromosomal translocations still predominantly relied on NHEJ despite DNA-PKcs inhibition. Furthermore, we observed that DNA-PKcs deletion resulted in an elevated utilization of microhomology in translocation formation. Nevertheless, NHEJ remained the primary mechanism driving translocation events.These findings provide valuable insights into the role of DNA-PKcs in the repair pathways involved in translocation events in human cell lines. The utilization of HTGTS allowed us to comprehensively analyze the effects of DNA-PKcs inhibition and deletion, shedding light on the interplay between NHEJ and alternative repair mechanisms in translocation formation.
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Project description:BRCA1/BARD1 is a macroH2A1-specific E3 ligase and implicates a role for macroH2A1 K123 ubiquitination in cellular senescence
2016-11-04 | MSV000080319 | MassIVE
Project description:MALT lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the NF-κB pathway. Gastric MALT lymphomas harboring such translocation do not respond to H. pylori eradication, while those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 24 MALT lymphomas (15 translocation-positive, 9 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-κB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions showed that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-κB target genes, particularly TLR6, CCR2, CD69 and BCL2, while translocation-negative cases were featured by active inflammatory and immune responses, such as IL8, CD86, CD28 and ICOS. Separate analyses of the genes differentially expressed between translocation-positive and negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10 mediated NF-κB activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors. This study compares MALT with other lymphomas namely follicular and mantle cell lymphomas, and investigates the molecular mechanisms of the lymphomagenesis between translocation positive versus negative MALT lymphoma cases in order to derive the pathways leading to MALT lymphoma pathogenesis using GSEA, GO, dynamic pathway analysis as well as other bioinformatics analysis. Samples were run on the Affymetrix HG-U133A and HG-U133 plus2 GeneChips.
2010-05-31 | E-GEOD-18736 | biostudies-arrayexpress
Project description:Escherichia coli is the most widely used bacterial model organism and is the most commonly used host for the expression of recombinant proteins. Here we describe an unexpected protein translocation phenomenon in E. coli, whereby over-expression of recombinant proteins leads to high-level lysis-independent, mechanosensitive channel (MscL) dependent release of recombinant protein into the periplasmic space. Protein accumulation in the periplasm leads to protein release into the extracellular environment, independent of outer membrane vesicle formation. The translocated proteins retain their corresponding biological activity, and can be isolated directly from the extracellular medium with high purity and yield. Condition-specific metabolomic and proteomic analyses combined with statistical enrichment analysis indicate a role of both osmotic and translational stress responses in the regulation of the MscL-dependent translocation phenomenon. We suggest a model coupling translational stress to the regulation of MscL via the action of both osmotic stress and the Alternative ribosome-rescue factor A (ArfA) to explain this potentially very useful phenomenon.
2018-03-02 | PXD006474 | Pride