Autosomal recessive PIK3CD deficiency
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE216493 | GEO | 2023/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:The Pik3cd null females are subfertile and have less growing follicles than their heterozygous littermates in the ovary. These mice poorly respond to the exogenous gonadotropins and ovulate much less oocytes than controls. In addition, the estrodial stimulated GC proliferation in preantral follicles is also impaired in Pik3cd null ovaries. FSH and E2 dramatically activates PI3K/AKT pathway in GCs of wild type mice, but not in the Pik3cd null mice. we used microarray to identify those genes regulated by Pik3cd in response to PMSG (Pregnant Mare Serum Gonadotropin) and E2 treatment in ovary. We set 3 treatment groups of both Pik3cd+/- and Pik3cd-/- female mice, including PD21 untreatment, PD21 after PMSG administration for 44 hours, PD21 after E2 administration for 72 hours, each group contained three biological repeats. The genes up/down-regulated significantly (not less than 2 fold change) in Pik3cd+/- mice after PMSG and E2 treatment were listed out as PMSG or E2 target genes, in which, those had not the same change trends in Pik3cd-/- were considered as Pik3cd-dependent genes.
2012-10-23 | E-GEOD-41746 | biostudies-arrayexpress
Project description:The Pik3cd null females are subfertile and have less growing follicles than their heterozygous littermates in the ovary. These mice poorly respond to the exogenous gonadotropins and ovulate much less oocytes than controls. In addition, the estrodial stimulated GC proliferation in preantral follicles is also impaired in Pik3cd null ovaries. FSH and E2 dramatically activates PI3K/AKT pathway in GCs of wild type mice, but not in the Pik3cd null mice. we used microarray to identify those genes regulated by Pik3cd in response to PMSG (Pregnant Mare Serum Gonadotropin) and E2 treatment in ovary.
2012-10-23 | GSE41746 | GEO
Project description:The underlying mechanisms of long non-coding RNAs (lncRNA) participating in the progression of lung cancers are largely unknown. We found a novel lncRNA, PIK3CD antisense RNA 2 (PIK3CD-AS2), that contributes to lung adenocarcinoma (LUAD) progression. The expression characteristics of PIK3CD-AS2 in LUAD were analyzed using microarray expression profile, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, and validated in 92 paired LUAD tissues by chromogenic in situ hybridization. Our data confirmed that PIK3CD-AS2 expression is a crucial regulator of LUAD progression and associated with shorter patient survival. In vitro studies showed that PIK3CD-AS2 increased cell growth and slowed apoptosis in p53wt cells but not in p53null cells. Mechanically, it is demonstrated that PIK3CD-AS2 bound to and maintained the stability of Y-box binding protein 1 (YBX1), a potent destabilizer of p53, by impeding its ubiquitination and degradation. Downexpression of YBX1 reversed PIK3CD-AS2-mediated inhibition of p53 signaling. Additionally, the therapeutic effect evaluation of a Locked Nuclear Acid (LNA) specifically targeting PIK3CD-AS2 showed an anti-tumor activity in mice with A549 cells xenograft and p53 wild-type LUAD patient-derived tumor xenograft (PDTX) model. Clinically, the high expression of PIK3CD-AS2 showed a poor disease-free survival in p53 wild-type patients in TCGA database. Our findings suggest that PIK3CD-AS2 regulates LUAD progression and elucidate a new PIK3CD-AS2/YBX1/p53 signaling axis, providing a potential lncRNA-directed therapeutic strategy especially in p53 wild-type LUAD patients.
2020-04-08 | GSE145018 | GEO
Project description:IL-21 induces B cell activation, and differentiation into antibody-secreting plasmblasts in vitro. This process is compromised in transitional B cells to gain of function mutations in PIK3CD We used microarrays to identify genes that are differentiatlly expressed following CD40L/IL-21 stimulation of human transitonal B cells from healthy donors and patients with GOF mutations in PIK3CD
2018-07-13 | GSE116999 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma in adults. The disease exhibits a striking heterogeneity in gene expression profiles and clinical outcomes, but its genetic causes remain to be fully defined. Through whole genome and exome sequencing, we characterized the genetic diversity of DLBCL. In all, we sequenced 73 DLBCL primary tumors (34 with matched normal DNA). Separately, we sequenced the exomes of 21 DLBCL cell lines. We identified 322 DLBCL cancer genes that were recurrently mutated in primary DLBCLs. We identified recurrent mutations implicating a number of known and not previously identified genes and pathways in DLBCL including those related to chromatin modification (ARID1A and MEF2B), NF-κB (CARD11 and TNFAIP3), PI3 kinase (PIK3CD, PIK3R1, and MTOR), B-cell lineage (IRF8, POU2F2, and GNA13), and WNT signaling (WIF1). We also experimentally validated a mutation in PIK3CD, a gene not previously implicated in lymphomas. The patterns of mutation demonstrated a classic long tail distribution with substantial variation of mutated genes from patient to patient and also between published studies. Thus, our study reveals the tremendous genetic heterogeneity that underlies lymphomas and highlights the need for personalized medicine approaches to treating these patients. 21 DLBCL cell lines and 70 DLBCL patient samples.
2013-01-23 | E-GEOD-43606 | biostudies-arrayexpress
Project description:Objective:mRNA sequencing of sorted naive CD4+ T cells from the spleens of PIK3CD GOF mice and WT littermate mice. Methods:Naive CD4+ T cells were negatively isolated ex vivo(Stemcell Technologies).Total RNA from isolated naive CD4+ T cells was extracted using RNeasy Plus Mini Kit (Qiagen, GmBH, Germany) according to the manufacture’s instruction and checked for RNA integrity by an Agilent Bioanalyzer 2100 (Agilent technologies, Santa Clara, US). Qualified total RNA was further purified by RNeasy micro kit (QIAGEN) and RNase-Free DNase Set (QIAGEN). Paired-end libraries were constructed using the TruSeq® RNA Sample Preparation Kit (Illumina, USA) according to the manufacturer’s instructions. The products are purified, enriched, quantified by Qubit® 2.0 Fluorometer (Life Technologies, USA) and validated by Agilent 2100 bioanalyzer to confirm insert size and calculate the mole concentration. Cluster was generated using cBot with the library diluted to 10 pM and then were sequenced on the Illumina HiSeq 2500 (Illumina, USA). The library construction and sequencing was performed at Shanghai Biotechnology Corporation (Shanghai, China). Results:Compared to the expression profiles for the WT cells, those for the mutant TNaive showed 2,307 genes with differential expression, of which 1,749 were upregulated and 558 were downregulated. Gene ontology analysis showed that PIK3CD GOF TNaive upregulated the expression of genes encoding molecules involved in the cell cycle and mitosis, including E2f1, E2f2, cyclin A2, cyclin B2, Cdk1, Hells and Nuf2, all of which might synergistically promote entry into the cycling phase. In addition, the genes encoding T cell activation, cytokines and cytokines receptors, chemokines and chemokine receptors, transcription factors, and metabolic regulators were differentially regulated in PIK3CD GOF mice compared to WT mice. Kyoto Encyclopedia of Genes and Genomes analysis showed that the altered genes in TNaive from PIK3CD GOF mice displayed significant enrichment of several sets associated with infection, inflammation and autoimmune disease Conlusion:PIK3CD GOF results in a loss of quiescence-associated gene expression patterns in naive T cells by collectively coupling the cell cycle, nutrient metabolism, cell trafficking and signal transduction.
2020-03-09 | GSE134322 | GEO
Project description:anti-CD3 + anti-CD46 stimulation for 2hr Patient has a mutation in CD46 that leads to reduced cell surface CD46 expression and suffers from episodes of atypical hemolytic uremic syndrome (aHUS), common variable immune deficiency (CVID) and recurrent infections
2015-06-01 | GSE69090 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma in adults. The disease exhibits a striking heterogeneity in gene expression profiles and clinical outcomes, but its genetic causes remain to be fully defined. Through whole genome and exome sequencing, we characterized the genetic diversity of DLBCL. In all, we sequenced 73 DLBCL primary tumors (34 with matched normal DNA). Separately, we sequenced the exomes of 21 DLBCL cell lines. We identified 322 DLBCL cancer genes that were recurrently mutated in primary DLBCLs. We identified recurrent mutations implicating a number of known and not previously identified genes and pathways in DLBCL including those related to chromatin modification (ARID1A and MEF2B), NF-κB (CARD11 and TNFAIP3), PI3 kinase (PIK3CD, PIK3R1, and MTOR), B-cell lineage (IRF8, POU2F2, and GNA13), and WNT signaling (WIF1). We also experimentally validated a mutation in PIK3CD, a gene not previously implicated in lymphomas. The patterns of mutation demonstrated a classic long tail distribution with substantial variation of mutated genes from patient to patient and also between published studies. Thus, our study reveals the tremendous genetic heterogeneity that underlies lymphomas and highlights the need for personalized medicine approaches to treating these patients.
2013-01-23 | GSE43606 | GEO
Project description:An 82-year-old woman with a history of LD stage SCLC of her left upper lobe nine years earlier, had been treated with five cycles chemotherapy cyclophosphamide, doxorubicin and etoposide (CDE)) resulting in a complete response. She received prophylactic cranial irradiation. Now she presented with a palpable mass in the right supra-clavicular fossa. Her further medical history revealed coronary vascular disease, for which she underwent PTCA; mild aortic valve stenosis and a pacemaker to treat a third degree AV block. She has NYHA class II. She had a history of cigarette smoking but she stopped when SCLC was diagnosed nine years ago. She had no dyspnea
2010-06-12 | GSE16575 | GEO
Project description:Recessive mutations in EXOSC3, encoding a subunit of the human RNA exosome complex, cause Pontocerebellar hypoplasia type 1b (PCH1B). We report a boy with severe muscular hypotonia, psychomotor retardation, progressive microcephaly, and cerebellar atrophy. Biochemical abnormalities comprised mitochondrial Complex I and PDHc deficiency. Whole exome sequencing uncovered a known EXOSC3-mutation p.(D132A) as the underlying cause. In patient fibroblasts, >50% of the EXOSC3 protein was trapped in the cytosol. mtDNA-copy numbers in muscle were reduced to 40%, but mutations in the mtDNA and nuclear mitochondrial genes were excluded. RNA-seq of patient muscle showed highly increased mRNA-copy numbers, especially for genes encoding structural subunits of OXPHOS-complexes I, III, and IV, possibly due to reduced degradation by a dysfunctional exosome complex. This is the first case of mitochondrial dysfunction associated with an EXOSC3 mutation, which expands the phenotypic spectrum of PCH1B. We discuss the links between exosome and mitochondrial dysfunction.
2017-08-22 | GSE99715 | GEO