Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using human induced pluripotent stem cell-derived oligodendrocytes to explore cellular phenotypes associated with t(1;11) translocation.

ABSTRACT: Although the underlying neurobiology of major mental illness (MMI) remains unknown, emerging evidence implicates a role for oligodendrocyte-myelin abnormalities. Here, we took advantage of a large family carrying a balanced t(1;11) translocation, which substantially increases risk of MMI, to undertake both diffusion tensor imaging (DTI) and cellular studies to evaluate the consequences of the t(1;11) translocation on white matter structural integrity and oligodendrocyte-myelin biology (this translocation disrupts among others the DISC1 gene which plays a crucial role in brain development). At a cellular level, we observe dysregulation of key pathways controlling oligodendrocyte development and morphogenesis in induced pluripotent stem cell (iPSC) case derived oligodendrocytes.

PROVIDER: EGAS00001004595 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Hikeshi-Mediated Nuclear Translocation of HSP70 Promotes Myelinogenesis by Preventing FBXW7-mediated Degradation of Sox10

Project description:Dysregulation of nucleocytoplasmic transport is intensively linked to many neurological diseases. Heat shock proteins 70 (HSP70s), which dramatically change its cellular localization upon stress, play important regulatory roles in nervous system. How the localization of HSP70s is regulated and the underlying physiological functions of this translocation are both poorly understood. Mutation in Hikeshi, encoding a nonconventional nuclear import carrier of HSP70s, lead to inherited leukodystrophy; however, the underlying mechanisms remain poorly understood. Here we showed that Hikeshi and HSP70s are essential for proper CNS myelination and remyelination. Loss of Hikeshi resulted in oligodendrocyte maturation arrest through preventing the nuclear translocation of HSP70s upon oligodendrocyte differentiation. HSP70s interacted with Sox10SOX10 in the nucleus and protected it from E3 ubiquitin ligase FBXW7-mediated ubiquitination degradation. Importantly, we discovered that the Hikeshi-dependent hyperthermia therapy, which induces nuclear import of HSP70s, promoted oligodendrocyte differentiation and remyelination following in vivo demyelinating injury. Overall, we demonstrate that Hikeshi-dependent nuclear translocation of HSP70s is essential for oligodendrocyte differentiation and myelinogenesis, and suggest the potential therapeutic value of hyperthermia therapy in myelin repair.

2023-02-19 | GSE225577 | GEO

Bacterial Translocation Markers as Predictors of Infectious and Inflammatory Complications in Acute Bowel Obstruction

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); 2. indirect method - the detection of serum lipopolysaccharide-binding protein (LBP) and presepsin (Soluble CD14 subtype or sCD14-ST). The aim of this study is to determine the diagnostic and prognostic significance of bacterial translocation as a predictor of the complications development in patients with malignant and benign acute bowel obstruction by assessing the relationship of biomarkers in the systemic circulation (LBP, sCD14-ST) with the detection of microorganism genes (16s rRNA) in mesenteric lymph nodes.

| 2403910 | ecrin-mdr-crc

ERCC6L2 suppresses chromosome translocation

Project description:ERCC6L2 suppresses chromosome translocation

| PRJNA1184159 | ENA

Characterize compounds that affect V(D)J recombination and chromsomal translocation using MP-HTGTS

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.

2023-12-30 | GSE242740 | GEO

TFE3 Xp11.2 translocation renal cell carcinoma mouse model

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.

2019-04-20 | GSE130072 | GEO

Transcriptome of JAZF1-SUZ12 translocation

Project description:Transcriptome of JAZF1-SUZ12 translocation

| PRJNA807168 | ENA

Stress modulates Ahi1-dependent nuclear localization of Ten-Eleven Translocation Protein 2

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.

2021-11-22 | GSE167344 | GEO

macroH2A is a BRCA1 ubiquitin ligase substrate

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

DNA-PKcs suppress chromosome translocation in human cells

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.

2023-09-01 | GSE232940 | GEO

ERCC6L2 suppresses chromosome translocation

Project description:ERCC6L2 is a recently characterized component in DNA damage repair. To investigate its function in chromosome translocation, 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 ERCC6L2 deletion. We quantified the number of translocation events by normalizing them to the number of rejoining events, denoted as TL. Interestingly, ERCC6L2 deletion led to an increase in TL, indicating a higher frequency of translocations.

2024-11-20 | GSE281505 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data