Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis.
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ABSTRACT:
PROVIDER: PRJNA704962 | ENA |
REPOSITORIES: ENA
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Project description:The human gastric epithelium forms highly organized gland structures with different subtypes of cells. The carcinogenic bacterium Helicobacter pylori can attach to gastric cells and subsequently translocate its virulence factor CagA, but the possible host cell tropism of H. pylori is currently unknown. Here, we report that H. pylori preferentially attaches to differentiated cells in the pit region of gastric units. Single-cell RNA-seq shows that organoid-derived monolayers recapitulate the pit region, while organoids capture the gland region of the gastric units. Using these models, we show that H. pylori preferentially attaches to highly differentiated pit cells, marked by high levels of GKN1, GKN2 and PSCA. Directed differentiation of host cells enable enrichment of the target cell population and confirm H. pylori preferential attachment and CagA translocation into these cells. Attachment is independent of MUC5AC or PSCA expression, and instead relies on bacterial TlpB-dependent chemotaxis towards host cell-released urea, which scales with host cell size.
2022-08-20 | GSE167561 | GEO
Project description:The human gastric epithelium forms highly organized gland structures with different subtypes of cells. The carcinogenic bacterium Helicobacter pylori can attach to gastric cells and subsequently translocate its virulence factor CagA, but the possible host cell tropism of H. pylori is currently unknown. Here, we report that H. pylori preferentially attaches to differentiated cells in the pit region of gastric units. Single-cell RNA-seq shows that organoid-derived monolayers recapitulate the pit region, while organoids capture the gland region of the gastric units. Using these models, we show that H. pylori preferentially attaches to highly differentiated pit cells, marked by high levels of GKN1, GKN2 and PSCA. Directed differentiation of host cells enable enrichment of the target cell population and confirm H. pylori preferential attachment and CagA translocation into these cells. Attachment is independent of MUC5AC or PSCA expression, and instead relies on bacterial TlpB-dependent chemotaxis towards host cell-released urea, which scales with host cell size.
| S-EPMC9535007 | biostudies-literature
Project description:The aim of the study is to evaluate Pit-1-induced genes in the MCF-7 cell line The Pit-1 transcription factor (also known as POU1F1) plays a critical role in cell differentiation during organogenesis of the anterior pituitary in mammals and is a transcriptional activator for pituitary gene transcription. Increased expression of Pit-1 has been reported in human tumorigenic breast cells. Here, we found that Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. In immunodeficient mice, Pit-1 overexpression induced tumoral growth and promoted metastasis in lung. In patients with invasive ductal carcinoma of the breast and node-positive tumors elevated expression of Pit-1 was significantly and independently associated with the occurrence of distant metastasis. These findings suggest that Pit-1 could help to make a more accurate prognosis in patients with node positive breast cancer and may represent a new therapeutic target (Journal of Clinical Investigation 2010, 120:4289-4302)
2014-12-12 | GSE64101 | GEO
Project description:ra05-09_urea - urea - What are the transcriptomic plant responses to urea nitrogen supply ? - Columbia Arabidopsis ecotype were grown hydroponically on 0.5 mM NH4NO3 as sole nitrogen source during 35 days under short days. Plants were then placed on 3 nutrient solutions supplemented, either with 1 mM NH4NO3, or with 0.5 mM NH4NO3 + 0.5 mM Urea, or with 1 mM Urea. Root and shoot samples were harvested separately 7 days after these different nitrogen treatments Keywords: treated vs untreated comparison
2007-10-16 | GSE9258 | GEO
Project description:Excess/residual urea is a pervasion problem in wine and Sake fermentation. We sought to reduce residual urea levels (to reduce ethyl carbamate leves) by engineering the Sake yeast strain K7 to constitutively express either the urea amidolyase (Dur1,2) or urea importer (Dur3). We sought to then compare the gene expression profiles of the metabolically engineered yeast strains to the parental strain during fermentation. Engineered strains would hopefully have gene expression profiles that were minimally different from the parental strain.
2010-04-21 | GSE17867 | GEO
Project description:Acute kidney disease caused by ischemia-reperfusion (IRI-AKI) is characterized by ectopic inflammation and tubular injury, in which macrophage infiltration and inflammatory activation play a critical pathogenic role. Calycosin is an active flavone from the root of Astragalus membranaceus and shows anti-inflammatory effects in various diseases. In this study, we investigated the renoprotective role of calycosin against IRI-AKI and the underlying mechanism. Our results showed that calycosin treatment reduced the levels of serum creatinine and urea nitrogen along with attenuated tubular necrosis and cast formation in IRI-AKI mice. Calycosin significantly suppressed the activation of NF-κB signaling and the expression of inflammatory mediators IL-1β and TNF-α in IRI-AKI kidneys. In vitro, calycosin inhibited LPS-induced inflammatory activation in RAW 264.7 cells. Interestingly, RNA-seq revealed that calycosin remarkably down-regulated chemotaxis-related pathways in RAW 264.7 cells. Among the differentially expressed genes, Ccl2/MCP-1, a critical chemokine mediating macrophage inflammatory chemotaxis, was down-regulated in both LPS-stimulated RAW 264.7 cells and IRI-AKI kidneys. Consistently, calycosin treatment attenuated macrophage infiltration in the IRI-AKI kidneys. Importantly, in combination with target prediction, molecular docking, and surface plasmon resonance, we showed that calycosin can directly bind to macrophage migration inhibitory factor (MIF). Functionally, calycosin abrogated MIF-stimulated NF-κB signaling activation and Ccl2 expression and MIF-mediated chemotaxis in RAW 264.7 cells without influencing its expression. Collectively, calycosin protects from IRI-AKI by suppressing MIF-mediated macrophage inflammatory chemotaxis. Calycosin could be a promising candidate medicine for clinical treatment of IRI-AKI.
2024-07-28 | GSE247263 | GEO
Project description:The aim of the study is to evaluate Pit-1-induced genes in the MCF-7 cell line The Pit-1 transcription factor (also known as POU1F1) plays a critical role in cell differentiation during organogenesis of the anterior pituitary in mammals and is a transcriptional activator for pituitary gene transcription. Increased expression of Pit-1 has been reported in human tumorigenic breast cells. Here, we found that Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. In immunodeficient mice, Pit-1 overexpression induced tumoral growth and promoted metastasis in lung. In patients with invasive ductal carcinoma of the breast and node-positive tumors elevated expression of Pit-1 was significantly and independently associated with the occurrence of distant metastasis. These findings suggest that Pit-1 could help to make a more accurate prognosis in patients with node positive breast cancer and may represent a new therapeutic target (Journal of Clinical Investigation 2010, 120:4289-4302) MCF-7 cells were transfected with the pcDNA3 (control, two samples as condition, named C1 and C2) or the pcDNA3-Pit-1 overexpression vector (two samples as condition, named 1+ and 2+) for 48 hours.
2014-12-12 | E-GEOD-64101 | biostudies-arrayexpress
Project description:Excess/residual urea is a pervasion problem in wine and Sake fermentation. We sought to reduce residual urea levels (to reduce ethyl carbamate leves) by engineering the Sake yeast strain K7 to constitutively express either the urea amidolyase (Dur1,2) or urea importer (Dur3). We sought to then compare the gene expression profiles of the metabolically engineered yeast strains to the parental strain during fermentation. Engineered strains would hopefully have gene expression profiles that were minimally different from the parental strain. Yeast strains were used to ferment Chardonnay grape must and total RNA harvested at 24 hrs into fermentation. 10 ug of total RNA was made into cDNA, and then labelled cRNA, with the Affymetrix GeneChip one cycle target amplification and labelling system. Fragmented cRNA was then hybridized to an Affymetrix YGS98 array in biological duplicate.
2010-05-07 | E-GEOD-17867 | biostudies-arrayexpress
Project description:Bitter pit is the most important physiological disorder affecting apples. In order to ascertain the genetic bases of its incidence in apple fruit, a mapping population of ‘Braeburn’ (susceptible to bitter pit) × ‘Cameo’ (resistant to bitter pit) cultivars was used to map the trait over two growing seasons. RNA-Seq on pools of RNA extracted from fruits of three resistant and three susceptible to bitter pit progenies at post-fertilization and full maturity stages, permitted us to identify a number of candidate genes underlying genetic resistance/susceptibility to bitter pit.
2018-06-12 | E-MTAB-6190 | biostudies-arrayexpress