Cord blood donor characteristics determine the efficacy of IL-15 armored CAR-transduced natural killer cells against CD19-positive B cell tumors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE233149 | GEO | 2023/12/19
REPOSITORIES: GEO
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Project description:The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. We examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly, and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromatin conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. We observed a number of CB-dependent gene positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
2016-03-21 | GSE77915 | GEO
Project description:The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. We examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly, and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromatin conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. We observed a number of CB-dependent gene positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
2016-03-21 | GSE77914 | GEO
Project description:The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. We examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly, and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromatin conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. We observed a number of CB-dependent gene positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
2016-03-21 | GSE77913 | GEO
Project description:The cell nucleus contains distinct biomolecular condensates that form at specific genetic loci, organize chromosomes in 3D space, and regulate RNA processing. Among these, Cajal bodies (CBs) require key “scaffolding” proteins for their assembly, which is not fully understood. Here we employ proximity biotinylation, mass spectrometry, and functional screening to comprehensively identify and test functions of CB components. We document 144 protein interactors of coilin, of which 70 were newly detected, and establish 25 players needed for CB assembly and/or maintenance. Surprisingly, depletion of nine coilin interactors – mostly constituents of the 60S ribosome (RPLs) – increased CB number and caused subdomains defined by coilin and the Survival of Motor Neuron protein (SMN) to merge. These phenotypes were traceable to altered nuclear levels of dimethylarginine. Our data implicate RPL24 and other players in the regulation of CBs by modulating post-translational modifications. Moreover, the prevalence of transcription factors among the identified components highlights roles for gene activity in CB assembly and nuclear positioning.
2024-11-10 | PXD042406 | Pride
Project description:We hypothesize that gene expression in the CBs of these two strains of mice are divergent thus contributing to the disparity in the phenotypes. More specifically, (1) genes related to CB function are expressed less in the A/J mice compared to DBA/2J mice; (2) gene expression levels of morphogenic and trophic factors of the CB maybe significantly lower in the A/J mice than the DBA/2J mice. In order to test these hypotheses, we utilized microarray analysis to examine transcriptional differences between CBs of both strains of mice. Keywords: comparative expression profiling
2006-12-02 | GSE5313 | GEO
Project description:Spliceosomal small nuclear RNAs (snRNAs) are modified by small Cajal body (CB) specific ribonucleoproteins (scaRNPs) to ensure snRNP biogenesis and pre-mRNA splicing. However, the function and subcellular site of snRNA modification are largely unknown. We show that CB localization of the protein Nopp140 is essential for concentration of scaRNPs in that nuclear condensate; and that phosphorylation by casein kinase 2 (CK2) at some 80 serines targets Nopp140 to CBs. Transiting through CBs, snRNAs are apparently modified by scaRNPs. Indeed, Nopp140 knockdown-mediated release of scaRNPs from CBs severely compromises 2’-O-methylation of spliceosomal snRNAs, identifying CBs as the site of scaRNP catalysis. Additionally, alternative splicing patterns change indicating that these modifications in U1, U2, U5, and U12 snRNAs safeguard splicing fidelity. Given the importance of CK2 in this pathway, compromised splicing could underlie the mode of action of small molecule CK2 inhibitors currently considered for therapy in cholangiocarcinoma, hematological malignancies, and COVID-19.
2021-07-01 | GSE173171 | GEO
Project description:To investigate location of Cajal bodies (CB) inside the cell nucleus, we created a stable cell line expressing the GFP version of CB-marker protein coilin at endogenous levels and performed ChIP-seq with anti-EGFP antibody. ChIP-seq revealed close association of CBs wih U3 genes, snRNA genes and histone genes in histone cluster 1 and 2.
2014-11-06 | GSE58449 | GEO
Project description:We hypothesize that gene expression in the CBs of these two strains of mice are divergent thus contributing to the disparity in the phenotypes. More specifically, (1) genes related to CB function are expressed less in the A/J mice compared to DBA/2J mice; (2) gene expression levels of morphogenic and trophic factors of the CB maybe significantly lower in the A/J mice than the DBA/2J mice. In order to test these hypotheses, we utilized microarray analysis to examine transcriptional differences between CBs of both strains of mice. Experiment Overall Design: . This study utilizes microarray analysis to test these hypotheses. Three sets of CBs were harvested from both strains. RNA was isolated and used for global gene expression profiling (Affymetrix Mouse 430 2.0 array). Statistically significant gene expression was determined as a minimum 6 counts of 9 pairwise comparisons, minimum 1.5-fold change, and p < 0.05.
2008-06-13 | E-GEOD-5313 | biostudies-arrayexpress
Project description:To investigate location of Cajal bodies (CB) inside the cell nucleus, we created a stable cell line expressing the GFP version of CB-marker protein coilin at endogenous levels and performed ChIP-seq with anti-EGFP antibody. ChIP-seq revealed close association of CBs wih U3 genes, snRNA genes and histone genes in histone cluster 1 and 2. 1 biological replicate of coilin ChIP-seq and input sample
2014-11-06 | E-GEOD-58449 | biostudies-arrayexpress
Project description:The carotid body (CB), located bilaterally at the carotid artery bifurcations, is the primary sensory organ for monitoring arterial blood O2 levels. Carotid bodies are immature at birth, exhibiting low sensitivity to hypoxia and become more sensitive with maturation during the first few weeks of neonatal life. To understand the molecular basis for the postnatal developmental hypoxic responses of CB, we isolated CBs from 5-day and 21-day-old Sprague Dawley rats, and performed RNA-sequencing, which allows comprehensive analysis of gene expression. Differentially expressed genes (DEGs) were generated using Edge R, while functional enrichment analysis was performed using GSEA. Analysis of RNA seq data showed 1769 DEGs of the total 12,696 genes shared between neonates and adults. Of the 1769 DEGs, 924 genes were upregulated, and 1680 genes were downregulated. Further analysis showed that genes related to oxidative phosphorylation (Ox/phos) and hypoxia-signaling pathways were significantly upregulated in neonatal compared to adult CBs, suggesting a possible link to differential developmental hypoxic responses seen in CB. Genes related to cytokine signaling (INF and TNFα) and transcription factors (CREB and NFB) mediated pathways were enriched in adult CBs suggesting expression of these pathways may be linked to developmental regulation. The RNA-seq results were verified by analyzing mRNA changes in selected genes by qRT-PCR. Our results of enrichment analysis of biological pathways offer a valuable insight into CB hypoxic sensing responses and development process.
2024-03-05 | GSE252955 | GEO