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Effect of DLBCL-associated NOTCH2 mutants on genomic RBP-J localization and H3K27 acetylation

ABSTRACT: Assessment of the genome-wide effect of DLBCL-asscociated NOTCH2 mutants in DLBCL on RBPJ and H3K27acetylation. DLBCL cell lines U2932 cells stably expressing HA-tagged NOTCH2(WT), NOTCH2(R2400*) or NOTCH2(Q2140*) were subjected to chromatin immnunoprecipitation DNA-sequencing (ChIP-seq) for RBP-J and H3K27ac.

ORGANISM(S): Homo sapiens

PROVIDER: GSE231623 | GEO | 2024/05/03

REPOSITORIES: GEO

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(1) Effect of KLHL6 loss on the transcriptome in DLBCL upon NOTCH ligand stimulation. (2) Effect of KLHL6 and NOTCH2 loss on the transcriptome in DLBCL. (3) Effect of DLBCL-associated NOTCH2 mutants on the transcriptome in DLBCL.

Project description:(1) Assessment of the transcriptional changes regulated by KLHL6 upon NOTCH ligand stimulation. Bulk RNA-seq in KLHL6 WT or KO U2932 cells was performed upon incubation with stromal OP9 cells stably expressing NOTCH ligand DLL1. (2) Assessment of the transcriptional changes regulated by the KLHL6-NOTCH2 axis in a xenotransplant model of DLBCL. Bulk RNA-seq was performed in in KLHL6+/+NOTCH2+/+(WT), KLHL6-/-NOTCH2+/+(K6-KO), KLHL6+/+NOTCH2-/-(N2-KO), KLHL6-/-NOTCH2-/-(DKO) U2932 cells xenotranplanted in NSG mice trated with CHOP. (3) Assessment of the transcriptional changes regulated by the DLBCL-associated NOTCH2 mutants. Bulk RNA-seq was performed inU2932 cells stably expressing NOTCH2(WT), NOTCH2(S2156A), NOTCH2(R2400*) or NOTCH2(Q2140*).

2024-05-03 | GSE231624 | GEO

Effect of DLBCL-associated NOTCH2 mutants on genomic RBP-J localization and H3K27 acetylation

Project description:Effect of DLBCL-associated NOTCH2 mutants on genomic RBP-J localization and H3K27 acetylation

| PRJNA967020 | ENA

Conditional ablation of the Notch2 receptor in the ocular lens

Project description:Notch signaling is essential for proper lens development, however the specific requirements of individual Notch receptors has not been previously investigated. Here we report the lens phenotypes of Notch2 conditionally mutant mice, which exhibited severe microphthalmia, reduced pupillary openings, disrupted fiber cell morphology, eventual loss of the anterior epithelium, fiber cell dysgenesis, and cataracts. Notch2 mutants also had a persistent lens stalk phenotype at E11.5, and aberrant DNA synthesis in the fiber cell compartment by E14.5. Gene expression analyses showed elevated levels of the cell cycle regulators Cdkn1a (p21Cip1), Ccnd2 (CyclinD2) and Trp63 (p63) that negatively regulates Wnt signaling. Although removal of Notch2 phenocopied the increased proportion of fiber cells of Rbpj and Jag1 conditional mutant lenses, Notch2 is not required for AEL proliferation, suggesting that a different receptor regulates this process. Instead, we found that the Notch2 normally blocks progenitor cell death. Overall, we conclude that Notch2-mediated signaling regulates lens morphogenesis, apoptosis, cell cycle withdrawal, and secondary fiber cell differentiation. We have compared gene expression of ocular lenses of mice that are lens specific conditional mutants of Notch2 gene to that of littermate controls that had no ablation of Notch2 gene in the lens. Two lenses of each of the three conditional mutants and controls were pooled together and total RNA was harvested from embryonic day 19.5 (E19.5) lenses. Gene expression changes caused by absence of Notch2 gene in the lens were analyzed.

2011-12-31 | E-GEOD-31643 | biostudies-arrayexpress

Conditional ablation of the Notch2 receptor in the ocular lens

2011-12-31 | GSE31643 | GEO

Project description:(1) Effect of KLHL6 loss on the transcriptome in DLBCL upon NOTCH ligand stimulation. (2) Effect of KLHL6 and NOTCH2 loss on the transcriptome in DLBCL. (3) Effect of DLBCL-associated NOTCH2 mutants on the transcriptome in DLBCL.

| PRJNA967024 | ENA

Monoclonal antibodies binding to different epitopes of CD20 differentially sensitizes DLBCL to different classes of chemotherapy

Project description:To investigate the differential gene expression profiles induced by rituximab and ofatumumab, we treated DLBCL cell lines U2932 and TMD8 with these monoclonal antibodies and analyzed their gene expression profiles

2023-04-07 | GSE228687 | GEO

NOTCH2 mutants

Project description:NOTCH2 mutants

| PRJNA967022 | ENA

Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine

Project description:Dendritic cells (DCs) in tissues and lymphoid organs comprise distinct functional subsets that differentiate in situ from circulating progenitors. Tissue-specific signals that regulate DC subset differentiation are poorly understood. We report that DC-specific deletion of the Notch2 receptor caused a reduction of DC populations in the spleen. Within the splenic CD11b+ DCs, Notch signaling blockade ablated a distinct population marked by high expression of adhesion molecule Esam. The Notch-dependent Esamhi DC subset also required lymphotoxin beta receptor signaling, proliferated in situ and facilitated efficient CD4+ T cell priming. The Notch-independent Esamlo DCs expressed monocyte-related genes and showed superior cytokine responses. In addition, Notch2 deletion led to the loss of CD11b+ CD103+ DCs in the intestinal lamina propria and to the corresponding decrease of IL-17-producing CD4+ T cells in the intestine. Thus,Notch2 is a common differentiation signal for T cell-priming CD11b+ DC subsets in the spleen and intestine. We compared genome-wide expression profiles of wild-type Esam(hi) and Esam(lo) splenic CD11b+ DC populations, along with CD11b+ DCs from DC-RBPJΔ mice. Spleens from 2-3 Cx3cr1-GFP+ RBPJflox/flox CD11c-Cre+ mice or Cx3cr1-GFP+ RBPJflox/flox Cre-negative littermate controls were isolated, pooled and depleted of lymphoid and erythroid cells by negative selection on MACS columns. Live cells were stained for surface expression of CD11c, CD11b and Esam. CD11c(hi) CD11b+ DCs from control mice could be separated into Esam(lo) GFP(hi) versus Esam(hi) GFP(lo) subsets. CD11c(hi) CD11b+ DCs from RBPJ-targeted mice spleens were uniformly Esam(lo) GFP(hi). The two subsets from control mice and single Esam(lo) GFP(hi) subset from RBPJ-targeted mice were sorted using FACSAria II flow sorter and analyzed using GeneChip Mouse Gene 1.0 ST Array (Affymetrix).

2011-10-31 | E-GEOD-31551 | biostudies-arrayexpress

DLBCL

Project description:DLBCL

| PRJNA1118307 | ENA

miRNA profiles of diffuse large B cell lymphoma (DLBCL) derived cell lines

Project description:miRNA profiling of human Diffuse Large B Cell Lymphoma (DLBCL) cell lines derived from the two main subtypes of this disease: Activated B Cell like (ABC-DLBCL) and Germinal Center B cell like (GCB-DLBCL), analyzing the 711 human miRNAs present in miRBase V10.0. Five ABC-like DLBCL cell lines (RIVA, Oci-Ly3, Oci-Ly10, HBL1 and U2932) and three GCB-like DLBCL cell lines (Oci-Ly7, Oci-Ly19 and SUDHL-6) were cultured in IMDM (Cellgro) with 20% human plasma, 1% penicillin/streptomycin/L-glutamine (Cellgro,) and 0,2% beta mercaptoethanol (Invitrogen). Total RNA was extracted from cell pellets using the mirVana™ miRNA Isolation Kit (Ambion), and sent to LC Sciences facility for microarray hybridization using microfluidics technology. FirstChoice® Human Skeletal Muscle Total RNA (Ambion) was used as common reference for all hybridizations. Background substracted and normalized data from each channel was used to calculate log ratios sample/reference. Keywords: miRNA profiling

2009-01-28 | GSE12933 | GEO

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