Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA98015 | ENA |
REPOSITORIES: ENA
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Project description:The aim was to investigate mechanisms contributing to quercetinâs previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anti-carcinogenic potency. In a 10-day experiment, 40 µM quercetin stabilized by 1mM ascorbate reduced Caco-2 differentiation up to 50% (P<0.001). Caco-2 RNA from days 5 and 10, hybridized on HG-U133A2.0 Affymetrix® GeneChips®, showed 1,743 affected genes on both days (P<0.01). All 14 Caco-2 differentiation-associated genes showed decreased expression (P<0.01), including intestinal alkaline phosphatase that was confirmed technically (qRT-PCR) and functionally (enzyme-activity). The 1,743 genes contributed to 27 affected pathways (P<0.05) categorized under 6 gene ontology (GO) processes, including apoptosis and cell-cycle. Genes within these GO-processes showed fold changes that suggest increased cell-survival and -proliferation. Furthermore, quercetin downregulated expression of genes involved in tumor-suppression and phase II metabolism, and upregulated oncogenes. Gene expression changes mediated by ascorbate-stabilized quercetin were concordant with those occurring in human colorectal carcinogenesis (â 80-90%), but were opposite to those previously described for Caco-2 cells exposed to quercetin in the absence of ascorbate (â 75-90%). In conclusion, gene expression among Caco-2 cells exposed to ascorbate-stabilized quercetin showed mechanisms contrary to what is expected for a cancer-preventive agent. Whether this unexpected in vitro effect is relevant in vivo, remains to be elucidated. Experiment Overall Design: Caco-2 cells were harvested on days 5 and 10 post-confluency. Per day, fold changes were calculated as quercetin vs. control.
2008-06-15 | E-GEOD-7259 | biostudies-arrayexpress
Project description:The aim was to investigate mechanisms contributing to quercetin’s previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anti-carcinogenic potency. In a 10-day experiment, 40 µM quercetin stabilized by 1mM ascorbate reduced Caco-2 differentiation up to 50% (P<0.001). Caco-2 RNA from days 5 and 10, hybridized on HG-U133A2.0 Affymetrix® GeneChips®, showed 1,743 affected genes on both days (P<0.01). All 14 Caco-2 differentiation-associated genes showed decreased expression (P<0.01), including intestinal alkaline phosphatase that was confirmed technically (qRT-PCR) and functionally (enzyme-activity). The 1,743 genes contributed to 27 affected pathways (P<0.05) categorized under 6 gene ontology (GO) processes, including apoptosis and cell-cycle. Genes within these GO-processes showed fold changes that suggest increased cell-survival and -proliferation. Furthermore, quercetin downregulated expression of genes involved in tumor-suppression and phase II metabolism, and upregulated oncogenes. Gene expression changes mediated by ascorbate-stabilized quercetin were concordant with those occurring in human colorectal carcinogenesis (≈ 80-90%), but were opposite to those previously described for Caco-2 cells exposed to quercetin in the absence of ascorbate (≈ 75-90%). In conclusion, gene expression among Caco-2 cells exposed to ascorbate-stabilized quercetin showed mechanisms contrary to what is expected for a cancer-preventive agent. Whether this unexpected in vitro effect is relevant in vivo, remains to be elucidated. Keywords: Colon cancer; Caco-2; quercetin; differentiation
2007-06-01 | GSE7259 | GEO
Project description:Glycosphingolipids of Caco-2 during differentiation
2020-07-25 | MSV000085829 | GNPS
Project description:Ascorbate (vitamin C) is an essential micronutrient in humans. The chronic severe deficiency of ascorbate, termed scurvy, has long been associated with increased susceptibility to infections. How ascorbate affects the immune system at the cellular and molecular levels remained unclear. Here, from a micronutrient screen, we identified ascorbate as a potent enhancer for antibody response by facilitating the IL-21/STAT3-dependent plasma cell differentiation in mouse and human B cells. The effect of ascorbate is unique, as other antioxidants failed to promote plasma cell differentiation. Ascorbate is critical during early B cell activation by poising the cells to plasma cell lineage without affecting the proximal IL-21/STAT3 signaling and the overall transcriptome. Consistent with its role as a cofactor for epigenetic enzymes, ascorbate potentiates plasma cell differentiation by remodeling the epigenome via TET (Ten Eleven Translocation), the enzymes responsible for DNA demethylation by oxidizing 5-methylcytosines into 5-hydroxymethylcytosine (5hmC). Genomewide 5hmC profiling identified ascorbate responsive elements (EAR) at the Prdm1 locus, including a distal element with a STAT3 motif overlapped with a CpG that was methylated and modified by TET in the presence of ascorbate. The results suggest that an adequate level of VC is required for antibody response and highlight how micronutrients can cooperate with epigenetic enzymes to regulate gene expression. Our finding also implies that epigenetic enzymes can function as sensors to gauge the availability of metabolites and influence cell fate decisions.
2022-09-06 | GSE206453 | GEO
Project description:Ascorbate (vitamin C) is an essential micronutrient in humans. The chronic severe deficiency of ascorbate, termed scurvy, has long been associated with increased susceptibility to infections. How ascorbate affects the immune system at the cellular and molecular levels remained unclear. Here, from a micronutrient screen, we identified ascorbate as a potent enhancer for antibody response by facilitating the IL-21/STAT3-dependent plasma cell differentiation in mouse and human B cells. The effect of ascorbate is unique, as other antioxidants failed to promote plasma cell differentiation. Ascorbate is critical during early B cell activation by poising the cells to plasma cell lineage without affecting the proximal IL-21/STAT3 signaling and the overall transcriptome. Consistent with its role as a cofactor for epigenetic enzymes, ascorbate potentiates plasma cell differentiation by remodeling the epigenome via TET (Ten Eleven Translocation), the enzymes responsible for DNA demethylation by oxidizing 5-methylcytosines into 5-hydroxymethylcytosine (5hmC). Genomewide 5hmC profiling identified ascorbate responsive elements (EAR) at the Prdm1 locus, including a distal element with a STAT3 motif overlapped with a CpG that was methylated and modified by TET in the presence of ascorbate. The results suggest that an adequate level of VC is required for antibody response and highlight how micronutrients can cooperate with epigenetic enzymes to regulate gene expression. Our finding also implies that epigenetic enzymes can function as sensors to gauge the availability of metabolites and influence cell fate decisions.
2022-09-06 | GSE183680 | GEO
Project description:Ascorbate (vitamin C) is an essential micronutrient in humans. The chronic severe deficiency of ascorbate, termed scurvy, has long been associated with increased susceptibility to infections. How ascorbate affects the immune system at the cellular and molecular levels remained unclear. Here, from a micronutrient screen, we identified ascorbate as a potent enhancer for antibody response by facilitating the IL-21/STAT3-dependent plasma cell differentiation in mouse and human B cells. The effect of ascorbate is unique, as other antioxidants failed to promote plasma cell differentiation. Ascorbate is critical during early B cell activation by poising the cells to plasma cell lineage without affecting the proximal IL-21/STAT3 signaling and the overall transcriptome. Consistent with its role as a cofactor for epigenetic enzymes, ascorbate potentiates plasma cell differentiation by remodeling the epigenome via TET (Ten Eleven Translocation), the enzymes responsible for DNA demethylation by oxidizing 5-methylcytosines into 5-hydroxymethylcytosine (5hmC). Genomewide 5hmC profiling identified ascorbate responsive elements (EAR) at the Prdm1 locus, including a distal element with a STAT3 motif overlapped with a CpG that was methylated and modified by TET in the presence of ascorbate. The results suggest that an adequate level of VC is required for antibody response and highlight how micronutrients can cooperate with epigenetic enzymes to regulate gene expression. Our finding also implies that epigenetic enzymes can function as sensors to gauge the availability of metabolites and influence cell fate decisions.
2022-09-06 | GSE183679 | GEO
Project description:Ascorbate (vitamin C) is an essential micronutrient in humans. The chronic severe deficiency of ascorbate, termed scurvy, has long been associated with increased susceptibility to infections. How ascorbate affects the immune system at the cellular and molecular levels remained unclear. Here, from a micronutrient screen, we identified ascorbate as a potent enhancer for antibody response by facilitating the IL-21/STAT3-dependent plasma cell differentiation in mouse and human B cells. The effect of ascorbate is unique, as other antioxidants failed to promote plasma cell differentiation. Ascorbate is critical during early B cell activation by poising the cells to plasma cell lineage without affecting the proximal IL-21/STAT3 signaling and the overall transcriptome. Consistent with its role as a cofactor for epigenetic enzymes, ascorbate potentiates plasma cell differentiation by remodeling the epigenome via TET (Ten Eleven Translocation), the enzymes responsible for DNA demethylation by oxidizing 5-methylcytosines into 5-hydroxymethylcytosine (5hmC). Genomewide 5hmC profiling identified ascorbate responsive elements (EAR) at the Prdm1 locus, including a distal element with a STAT3 motif overlapped with a CpG that was methylated and modified by TET in the presence of ascorbate. The results suggest that an adequate level of VC is required for antibody response and highlight how micronutrients can cooperate with epigenetic enzymes to regulate gene expression. Our finding also implies that epigenetic enzymes can function as sensors to gauge the availability of metabolites and influence cell fate decisions.
2022-09-06 | GSE206452 | GEO
Project description:This study explores how quercetin may treat endometriosis (EMs) by combining network pharmacology and transcriptome sequencing approaches. Through network pharmacology, 132 shared targets between quercetin and EMs were identified, with KEGG pathway analysis suggesting that the MAPK signaling pathway could be a significant therapeutic target. Transcriptome sequencing revealed that PDGFRB was highly expressed in ectopic endometrial tissue, a finding confirmed by immunohistochemistry (IHC) showing elevated levels of PDGFRB, RAS, RAF1, and ERK1/2 in ectopic lesions. In an EMs mouse model, quercetin treatment led to a marked reduction in ectopic lesion volume, lowered adhesion scores, and decreased expression of PDGFRB, RAS, RAF1, and ERK1/2 in endometrial tissues. Additionally, the knockdown of PDGFRB in endometriosis cells inhibited their proliferation, invasion, and migration, processes critical to EMs pathology. Quercetin treatment further suppressed cell viability and downregulated the protein expression of RAS, phosphorylated RAF1, RAF1, phosphorylated ERK, and ERK1/2. These findings collectively suggest that quercetin exerts its therapeutic effect in endometriosis by regulating the MAPK signaling pathway via PDGFRB, thereby reducing EMs cell proliferation, invasion, and migration. This study provides insights into quercetin’s multi-targeted mechanism of action in endometriosis treatment.
2024-11-16 | GSE281569 | GEO
Project description:Single cell clonal analysis identifies an AID-dependent pathway of plasma cell differentiation
| PRJNA784455 | ENA