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Synertistic effects of Arid1a inactivation and oncogenic Kras mutation on chromatin accessbility in mouse embryonic cells (MEFs)

ABSTRACT: To explore mechanisms underlying the cooperative effect in the proliferative phenotype, we harvest MEFs of different genotypes (KA, K, A, WT) recombined and un-recombined.

ORGANISM(S): Mus musculus

PROVIDER: GSE207888 | GEO | 2022/09/05

REPOSITORIES: GEO

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Synertistic effects of Arid1a inactivation and oncogenic Kras mutation on gene expression in mouse embryonic cells (MEFs)

Project description:To explore transcriptomic mechanisms underlying the cooperative effect in the proliferative phenotype, we harvest MEFs of different genotypes (KA, K, A, WT) recombined and un-recombined. We performed RNA-seq analysis on 5 recombined (Ad-CMV-Cre) cell lines of each genotypic conditions (WT, Arid1a L/L , Kras-LSL-G12D, and Kras-LSL-G12D; Arid1a L/L) as well as 2 or 3 un-recombined (Ad-CMV-GFP) or mock-infected MEF cell lines.

2022-09-05 | GSE207891 | GEO

IKK alpha inactivation impairs early B-lymphopoiesis during hematopoiesis

Project description:IKKa, a major regulator of noncanonical and canonical NF-kB pathways, is essential for B-lymphocyte maturation and secondary lymph organ formation. No evidence of IKKa regulating early B cell development currently exists. Here we found reduced pre-pro-B and pro-B cells but increased myeloid-erythroid lineages in the bone marrow (BM) of knockin mice expressing reduced and kinase-dead IKKa (KA/KA). The KA/KA BM cells recaptured their defects in wild-type recipients and KA/KA fetal liver displayed reduced B cells but increased progenitors. IKKa inactivation impaired both NF-kB pathways and deregulated expression of many genes required for early B cell commitment and hematopoiesis, including downregulated Pax5, IRF4, and Ikaros expression, but increased C/EBPa, GATA1, and Stat3 levels. Reintroduced combined NF-kB components, Pax5, and IKKa promoted BM B cell differentiation and repressed myeloid-erythroid lineages. Our studies revealed a new function of IKKa in a coordinated development process of B-lineage and erythroid-myeloid lineages during hematopoiesis via multiple pathways. Microarray analysis was performed on RNA isolated from the BM of B220+ cells isolated from 4-week old WT and KA/KA mice using affymetrix mouse 430 2.0 array chip, containing 45,000 genes, at the Laboratory of Molecular Technology SAIC-Frederick. Data were normalized, and log2 transformations were generated using Partek software (St. Louis, MO, USA).

2011-07-02 | E-GEOD-30363 | biostudies-arrayexpress

Arid1a restrains Kras-dependent changes in acinar cell identity.

Project description: Not available

| S-EPMC6050044 | biostudies-literature

Synergistic effects of Arid1a inactivation and oncogenic Kras mutation in mouse embryonic cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-09-05 | GSE207895 | GEO

Inactivation of Arid1a in the endometrium is associated with endometrioid tumorigenesis through transcriptional reprogramming.

Project description: Not available

| S-EPMC7264300 | biostudies-literature

ARID1A facilitates KRAS signaling-regulated enhancer activity in an AP1-dependent manner in colorectal cancer cells.

Project description: Not available

| S-EPMC6585056 | biostudies-literature

Gene expression alteration by macrophage depletion in IKKα mutant mice

Project description:We generated Ikkα-KA/KA knock-in mice (KA/KA), in which an ATP binding site of Ikkα Lys 44 was replaced by alanine. The knock-in mice develop severe skin lesions and begin to die after 6 to 10 months. We also found lung SCCs in some of the mice. To study lung SCC development, we stabilize the skin condition by crossing KA/KA with Lori.Ikkα transgenic mice to generate KA/KA-Lori.Ikkα mice, which 100% spontaneously developed lethal lung SCC at 4 to 6 months of age. Clodronate-liposomes obtained from Dr. N. van Rooijen (Vrije Universiteit, Amsterdam, Netherlands) were intravenously injected into mice twice every week, started in 4 weeks old mice, and continued for 3 months. The dose of clodronate-liposomes was 100µl during the first month and elevated to 150 100µl after that. The depletion efficacy was confirmed by detecting pulmonary macrophages with Flow Cytometry. Depletion of macrophages in these KA/KA-Lori.Ikkα mice could significantly reduce inflammation and prevent lung SCC developmrnt. This aim of this microarray assay is to identify differentially expressed genes among Wild type, KA/KA-Lori.Ikkα, and macophage-depleted KA/KA-Lori.Ikkα mice, which may highlight the important genes or parthways involved in inflammation-associated lung SCC carcinogenesis.

2012-05-01 | GSE37655 | GEO

Transcriptome Profiling of Hippocampal CA1 After Early Life Seizure-Induced Preconditioning May Elucidate New Genetic Therapies for Epilepsy

Project description:Injury of the CA1 subregion induced by a single injection of kainic acid (1×KA) is attenuated when juvenile animals (P20) have a history of two sustained neonatal seizures on P6 and P9. To identify gene candidates involved in the spatially protective effects produced by early life conditioning seizures, we profiled and compared the transcriptomes of CA1 subregions from control, 1×KA, and 3×KA treated animals. More genes were regulated following 3×KA (9.6%) than after 1×KA (7.1%). Following 1×KA, genes supporting oxidative stress, growth, development, inflammation, and neurotransmission were upregulated (e.g., Cacng1, Nadsyn1, Kcng1, Aven, S100a4, GFAP, Vim, Hrsp12, Grik1). After 3×KA, protective genes were differentially over-expressed (e.g., Cat, Gpx7, GAD1, Hspa12A, Foxn1, adenosine A1 receptor, Ca2+ adaptor and homeostatic proteins, Cacnb4, Atp2b2, anti-apoptotic Bcl-2 gene members, intracellular trafficking protein, Grasp, suppressor of cytokine signaling (Socs3)). Distinct anti-inflammatory interleukins not observed in adult tissues (e.g., IL6 transducer, IL23 and IL33 or their receptors (ILF2)) were also over-expressed. Several transcripts were validated by real-time polymerase chain reaction (QPCR) and immunohistochemistry. QPCR showed that casp 6 was increased after 1×KA but reduced after 3×KA; pro-inflammatory gene cox1 was either upregulated or unchanged after 1×KA but reduced by ~70% after 3×KA. Enhanced GFAP immunostaining following 1×KA was selectively attenuated in the CA1 subregion after 3×KA. The observed differential transcriptional responses may contribute to early life seizure-induced pre-conditioning and neuroprotection by reducing glutamate receptor-mediated Ca2+ permeability of the hippocampus and redirecting inflammatory and apoptotic pathways which could lead to new genetic therapies for epilepsy.

2013-02-14 | GSE44031 | GEO

Gene expression alteration by macrophage depletion in IKKα mutant mice

2012-04-30 | E-GEOD-37655 | biostudies-arrayexpress

Single-PanIN-seq unveils that <i>ARID1A</i> deficiency promotes pancreatic tumorigenesis by attenuating <i>KRAS</i>-induced senescence.

Project description: Not available

| S-EPMC8203294 | biostudies-literature