Hepatocyte-specific knock-out of Nfib aggravates hepatocellular tumorigenesis via enhancing urea cycle
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PROVIDER: PRJNA826111 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: Nuclear Factor I B (NFIB) has been reported to promote tumor growth, metastasis, and liver regeneration, but its mechanism in liver cancer is not fully elucidated. The present study aims to reveal the role of NFIB in hepatocellular carcinogenesis Methods:In our study, we constructed hepatocyte-specific NFIB gene knockout mice with CRISPR/Cas9 technology (Nfib-/-; Alb-cre), and induced liver cancer mouse model by intraperitoneal injection of DEN/CCl4 Results: First, we found that Nfib-/-; Alb-cre mice developed more tumor nodules and had heavier livers than wild-type mice. H&E staining indicated that the liver histological severity of Nfib-/- group was more serious than that of WT group. Then we found that the differentially expressed genes in the tumor tissue between Nfib-/- mice and wild type mice were enriched in urea cycle. Furthermore, ASS1 and CPS1, the core enzymes of the urea cycle, were significantly upregulated in Nfib-/- tumors. Subsequently, we validated that the expression of ASS1 and CPS1 increased after knockdown of NFIB by lentivirus in normal hepatocytes and also promoted cell proliferation in vitro. In addition, ChIP assay confirmed that NFIB can bind with promoter region of both ASS1 and CPS1 gene Conclusions:Our study reveals for the first time that hepatocyte-specific knock-out of Nfib aggravates hepatocellular tumor development by enhancing the urea cycle.
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Project description:NFIB is a transcription factor that can both positively and negatively regulate gene transcription. We have identified NFIB as an arginine methylation substrate of CARM1. To elucidate how CARM1 could regulate NFIB target genes by methylating NFIB, we performed this ChIP-seq to firstly identify NFIB direct binding gengs.
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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
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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:Hepatocyte-like cells (HLCs) are derived from human pluripotent stem cells (hPSCs) in vitro, but differentiation protocols commonly give rise to a heterogeneous mixture of cells. This variability confounds the evaluation of in vitro functional assays performed using HLCs. We demonstrate the purification of a sub-population of functional HLCs differentiated from multiple hPSC lines using the hepatocyte surface marker Asialoglycoprotein Receptor 1 (ASGR1). We analyzed the expression profile of ASGR1-positive cells by microarray, and tested their ability to perform mature hepatocyte functions (albumin and urea secretion, cytochrome activity). By these measures, ASGR1-positive HLCs are enriched for the gene expression profile and functional characteristics of primary hepatocytes compared to unsorted HLCs.
2016-01-22 | GSE77086 | GEO
Project description:This project identified NFI family members as CARM1 substrates. NFIB was previously reported to play a critical role in the development of small cell lung cancer. We provided evidence that the arginine methylation of NFIB is required for its oncogenic function in small cell lung cancer.
2023-02-07 | PXD038237 | Pride
Project description:To identify direct NFIB target genes in HFSCs, we performed chromatin immunoprecipitation and deep sequencing (ChIP-seq) analysis using FACS-isolated HFSCs. Two independent NFIB ChIP-seq experiments were conducted.
2013-02-07 | E-GEOD-42900 | 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:Although urea is the most used nitrogen fertilizer worldwide, little is known on the capacity of crop plants to use urea per se as a nitrogen source for development and growth. To date, the molecular and physiological bases of its transport have been investigated only in a limited number of species. In particular, up to date only one study reported the transcriptomic modulation induced by urea treatment in the model plant Arabidopsis (MM-CM-)rigout et al., 2008 doi: 10.1104/pp.108.119339). In maize, one of crops using huge amount of urea, only a physiological characterization of uptake and assimilation of the N-source has been conducted. General aim of the present work was the comprehension of the molecular basis of urea uptake and assimilation in maize plants, using a transcriptomic approach. In addition, the work focused on the possible interactions between the two main N-sources, conceivably occurring concomitantly in the soil, urea and nitrate. 5 dd-old maize plants were treated for 8 hours with nutrient solution containing nitrogen in form of urea; nitrate; urea and nitrate; or not exposed to any form of nitrogen. Three different biological replicates were used for each sample repeating the experiment three times. All samples were obtained pooling roots of six plants.
2015-03-02 | E-GEOD-53102 | biostudies-arrayexpress
Project description:Although urea is the most used nitrogen fertilizer worldwide, little is known on the capacity of crop plants to use urea per se as a nitrogen source for development and growth. To date, the molecular and physiological bases of its transport have been investigated only in a limited number of species. In particular, up to date only one study reported the transcriptomic modulation induced by urea treatment in the model plant Arabidopsis (Mérigout et al., 2008 doi: 10.1104/pp.108.119339). In maize, one of crops using huge amount of urea, only a physiological characterization of uptake and assimilation of the N-source has been conducted. General aim of the present work was the comprehension of the molecular basis of urea uptake and assimilation in maize plants, using a transcriptomic approach. In addition, the work focused on the possible interactions between the two main N-sources, conceivably occurring concomitantly in the soil, urea and nitrate.
2015-03-02 | GSE53102 | GEO