Gene expression changes by Foxo1 knockdown in primary human dermal lymphatic endothelial cells (HDLEC)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE142608 | GEO | 2020/01/07
REPOSITORIES: GEO
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Project description:Gene expression changes by Foxo1 knockdown in primary human dermal lymphatic endothelial cells (HDLEC)
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Project description:C2C12 mouse myoblasts were transduced with either PAX3-FOXO1 expression vector (P3F-C2C12), a system that is commonly used to study the more aggressive alveolar rhabdomyosarcoma subtype, or empty vector (Ctrl-C2C12). Exosomes were isolated from both cell lines by differential centrifugation, and exosomal markers were characterized by western blot. Then, the Affymetrix GeneChip miRNA 3.0 array was used to identify the miRNA content of the extracted exosomes where the differentially deregulated miRNA (either enriched or depleted) in P3F-C2C12 exosomes were determined relative to Ctrl-C2C12 exosomes. Results showed that PAX3-FOXO1 fusion gene alters the content of exosomes and that the enriched miR-486-5p is a downstream effector of PAX3-FOXO1 in mediating the oncogenic effects of exosome-mediated paracrine signaling in this setting.
2019-12-01 | E-MTAB-7646 | biostudies-arrayexpress
Project description:The pathways regulating the formation of the germinal center (GC) dark- (DZ) and light- (LZ) zones are unknown. We show that FOXO1 expression is restricted to the GC DZ and is required for DZ formation, since its absence in mice leads to the complete loss of DZ gene programs and the formation of LZ-only GCs. FOXO1-negative GC B-cells display normal somatic hypermutation, but defective affinity maturation and class switch recombination. The function of FOXO1 in sustaining the DZ program involves the transactivation of the chemokine receptor CXCR4, and the cooperation with BCL6 in the trans-repression of genes involved in immune activation, DNA-repair and plasma cell differentiation. These results have also implications for understanding the role of FOXO1 mutations in lymphomagenesis. We used microarrays to determine the consequences of FOXO1 deletion in the GC B cell comparment, and correlate these data with phenotypic changes GC B cell subpopulations were collected by Fluorescence Activated Cell Sorting (FACS) from B cell enriched fractions of splenic mononuclear cell pools (12 days after SRBC immunization). 20ng of total RNA (RIN>9) for each sample was used as a template for linear cDNA amplification (Ovation RNA amplification Kit, NuGen). cDNA was labeled using the Encore Biotin Labeling Kit (NuGen) and hybridized to Affymetrix Mouse 430.2 gene expression arrays
2015-12-04 | E-GEOD-69216 | biostudies-arrayexpress
Project description:Analysis of transcriptional changes upon silencing of endothelial VEGF. Because transcription factor Foxo1 levels increase under VEGF silencing, we hypothesized that Foxo1 transcriptional activity would be apparent in a whole-genome microarray. Double-silencing of VEGF+Foxo1 was also performed to determine which transcriptional changes are Foxo1-dependent in a VEGF-deficient background.
2015-12-31 | E-MTAB-2515 | biostudies-arrayexpress
Project description:The pathways regulating the formation of the germinal center (GC) dark- (DZ) and light- (LZ) zones are unknown. We show that FOXO1 expression is restricted to the GC DZ and is required for DZ formation, since its absence in mice leads to the complete loss of DZ gene programs and the formation of LZ-only GCs. FOXO1-negative GC B-cells display normal somatic hypermutation, but defective affinity maturation and class switch recombination. The function of FOXO1 in sustaining the DZ program involves the transactivation of the chemokine receptor CXCR4, and the cooperation with BCL6 in the trans-repression of genes involved in immune activation, DNA-repair and plasma cell differentiation. These results have also implications for understanding the role of FOXO1 mutations in lymphomagenesis. We used microarrays to determine the consequences of FOXO1 deletion in the GC B cell comparment, and correlate these data with phenotypic changes
2015-12-04 | GSE69216 | GEO
Project description:VEGF induces elongation of endothelial cells (ECs) that are derived from wild-type (Foxo1(+/+)) ES cells. VEGF-induced EC elongation is an important process of angiogenesis. ECs derived from Foxo1(-/-) ES cells fail to elongate in response to VEGF. Gene expression profiling of wild-type and Foxo1(-/-) ECs in the presence or absence of VEGF stimulation identifies responsible genes that regulate EC elongation. One wild-type (Foxo1(+/+)) ES cell clone and one Foxo1(-/-) ES cell clone were used. ES cells were cultured on OP9 stromal cell layer in the presence or absence of VEGF (10 ng/ml). After 6.5 days, VE-cadherin+ CD31+ ECs were isolated by FACS and used for total RNA extraction. Three independent experiments were performed for each condition.
2016-02-16 | E-GEOD-76366 | biostudies-arrayexpress
Project description:Strict regulation of proliferation is vital for development, whereas unregulated cell proliferation is a fundamental characteristic of cancer. The polarity protein atypical protein kinase C lambda/iota (aPKC lambda) is associated with cell proliferation through unknown mechanisms. In endothelial cells, suppression of aPKC lambda impairs proliferation despite hyperactivated mitogenic signaling. Here we show that aPKC lambda phosphorylates the DNA binding domain of forkhead box O1 (FoxO1) transcription factor, a gatekeeper of endothelial growth. Although mitogenic signaling excludes FoxO1 from the nucleus, consequently increasing c-Myc abundance and proliferation, aPKC lambda controls c-Myc expression via FoxO1/miR-34c signaling without affecting its localization. We find this pathway is strongly activated in the malignant vascular sarcoma, angiosarcoma, and aPKC inhibition reduces c-Myc expression and proliferation of angiosarcoma cells. Moreover, FoxO1 phosphorylation at Ser218 and aPKC expression correlates with poor patient prognosis. Our findings may provide a new therapeutic strategy for treatment of malignant cancers, like angiosarcoma.
2019-11-12 | PXD011595 | Pride
Project description:To identify genes regulated by FOXO1, we performed RNA-seq analysis of human unbilical vein endothelial cells (HUVECs) overexpressing CA-FOXO1 by adenovirus. CA-FOXO1 is constructed by mutating three amino-acids phosphorylated by Akt, T24, S256, and S319, and is constitutively localized in the nucleus compared to wild-type FOXO1.
2024-03-01 | GSE220503 | GEO
Project description:PI3K signaling and FOXO transcription factors play opposing roles at several B cell developmental stages. We show here abundant nuclear FOXO1 expression in the proliferative compartment of the germinal center (GC), its dark zone (DZ), and PI3K activity, downregulating FOXO1, in the GC light zone (LZ), where cells are selected for further differentiation. However, here FOXO1 is expressed in c-Myc+ cells destined for DZ reentry. Upon FOXO1 ablation by genetic means or induction of PI3K activity GCs become devoid of their DZ, due at least partly to the downregulation of the chemokine receptor CXCR4. While this is known to prevent proper cyclic selection of cells expressing high-affinity antibodies, the initiation of immunoglobulin switching is essentially dependent on FOXO1 activity. All samples were obtained from mouse germinal center (GC) B cells (Cgamma1-cre; YFP, P110*, FOXO1 f/f or PTEN f/f animals). Cells used for microarray analysis were FACS sorted cells.
2015-11-23 | E-GEOD-68043 | biostudies-arrayexpress
Project description:Tight regulation of Toll-like receptor (TLR)-mediated inflammatory responses is important in innate immunity. Here, we show that T cell death-associated gene 51 (TDAG51/PHLDA1) is a novel coactivator of the transcription factor FoxO1, regulating inflammatory mediator production in the lipopolysaccharide (LPS)-induced inflammatory response. TDAG51 induction by LPS stimulation was mediated by the TLR2/4 signaling pathway in bone marrow-derived macrophages (BMMs). LPS-induced inflammatory mediator production was significantly decreased in TDAG51-deficient BMMs. In TDAG51-deficient mice, LPS- or pathogenic Escherichia coli infection-induced lethal shock was reduced by decreasing serum proinflammatory cytokine levels. The recruitment of 14-3-3 to FoxO1 was competitively inhibited by the TDAG51-FoxO1 interaction, leading to blockade of FoxO1 cytoplasmic translocation and thereby strengthening FoxO1 nuclear accumulation. TDAG51/FoxO1 double-deficient BMMs showed significantly reduced inflammatory mediator production compared with TDAG51- or FoxO1-deficient BMMs. TDAG51/FoxO1 double deficiency protected mice against LPS- or pathogenic E. coli infection-induced lethal shock by weakening the systemic inflammatory response. Thus, these results indicate that TDAG51 acts as a coactivator of the transcription factor FoxO1, leading to strengthened FoxO1 activity in the LPS-induced inflammatory response.
2023-06-24 | PXD039815 | Pride