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https://www.readbyqxmd.com/read/29339095/patterning-the-gastrointestinal-epithelium-to-confer-regional-specific-functions
#1
REVIEW
Cayla A Thompson, Ann DeLaForest, Michele A Battle
The gastrointestinal (GI) tract, in simplest terms, can be described as an epithelial-lined muscular tube extending along the cephalocaudal axis from the oral cavity to the anus. Although the general architecture of the GI tract organs is conserved from end to end, the presence of different epithelial tissue structures and unique epithelial cell types within each organ enables each to perform the distinct digestive functions required for efficient nutrient assimilation. Spatiotemporal regulation of signaling pathways and downstream transcription factors controls GI epithelial morphogenesis during development to confer essential regional-specific epithelial structures and functions...
January 12, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29328449/bioinformatics-analysis-to-screen-key-genes-implicated-in-the-differentiation-of-induced-pluripotent-stem-cells-to-hepatocytes
#2
Rui Lin, Yufeng Wang, Kun Ji, Zhongyan Liu, Shuai Xiao, Dehua Zhou, Quanning Chen, Baomin Shi
Due to the lack of potential organs, hepatocellular transplantation has been considered for treating end-stage liver disease. Induced pluripotent stem cells (iPSCs) are reverted from somatic cells and are able to differentiate into hepatocytes. The present study aimed to investigate the mechanisms underlying iPSC differentiation to hepatocytes. GSE66076 was downloaded from the Gene Expression Omnibus; this database includes data from 3 undifferentiated (T0), 3 definitive endoderm (T5), and 3 early hepatocyte (T24) samples across hepatic‑directed differentiation of iPSCs...
January 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328431/bioinformatic-analysis-of-gene-expression-profiling-of-intracranial-aneurysm
#3
Lijuan Bo, Bo Wei, Zhanfeng Wang, Chaohui Li, Zheng Gao, Zhuang Miao
Intracranial aneurysm (IA) is a severe clinical condition of primary concern and currently, there is no effective therapeutic reagent. The present study aimed to investigate the molecular mechanism of IA via bioinformatic analysis. Various gene expression profiles (GSE26969) were downloaded from the Gene Expression Omnibus database, including 3 IA and 3 normal superficial temporal artery samples. Firstly, the limma package in R language was used to identify differentially expressed genes (DEGs; P‑value <0...
December 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29306027/trichloroethylene-perturbs-hnf4a-expression-and-activity-in-the-developing-chick-heart
#4
Alondra P Harris, Kareem A Ismail, Martha Nunez, Ira Martopullo, Alejandro Lencinas, Ornella I Selmin, Raymond B Runyan
Exposure to trichloroethylene (TCE) is linked to formation of congenital heart defects in humans and animals. Prior interactome analysis identified the transcription factor, Hepatocyte Nuclear Factor 4 alpha (HNF4a), as a potential target of TCE exposure. As a role for HNF4a is unknown in the heart, we examined developing avian hearts for HNF4a expression and for sensitivity to TCE and the HNF4a agonist, Benfluorex. In vitro analysis using a HNF4a reporter construct showed both TCE and HFN4a to be antagonists of HNF4a-mediated transcription at the concentrations tested...
January 3, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29298995/nuclear-receptor-gene-polymorphisms-and-warfarin-dose-requirements-in-the-quebec-warfarin-cohort
#5
Payman Shahabi, Félix Lamothe, Stéphanie Dumas, Étienne Rouleau-Mailloux, Yassamin Feroz Zada, Sylvie Provost, Geraldine Asselin, Ian Mongrain, Diane Valois, Marie-Josée Gaulin Marion, Louis-Philippe Lemieux Perreault, Sylvie Perreault, Marie-Pierre Dubé
Warfarin is primarily metabolized by cytochrome 2C9, encoded by gene CYP2C9. Here, we investigated whether variants in nuclear receptor genes which regulate the expression of CYP2C9 are associated with warfarin response. We used data from 906 warfarin users from the Quebec Warfarin Cohort (QWC) and tested the association of warfarin dose requirement at 3 months following the initiation of therapy in nine nuclear receptor genes: NR1I3, NR1I2, NR3C1, ESR1, GATA4, RXRA, VDR, CEBPA, and HNF4A. Three correlated SNPs in the VDR gene (rs4760658, rs11168292, and rs11168293) were associated with dose requirements of warfarin (P = 2...
January 3, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29280746/congenital-hyperinsulinism-diagnosis-and-treatment-update
#6
Hüseyin Demirbilek, Khalid Hussain
Pancreatic β-cells are finely tuned to secrete insulin so that plasma glucose levels are maintained within a narrow physiological range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is the inappropriate seretion of insulin in the presence of low plasma glucose levels and leads to severe and persistent hypoglycaemia in neonates and children. Mutations in 12 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2) that are involved in the regulation of insulin secretion from pancreatic β-cells have been described to be responsible for the underlying molecular mechanisms leading to congenital HH...
December 27, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29272997/genome-variation-and-conserved-regulation-identify-genomic-regions-responsible-for-strain-specific-phenotypes-in-rat
#7
David Martín-Gálvez, Denis Dunoyer de Segonzac, Man Chun John Ma, Anne E Kwitek, David Thybert, Paul Flicek
BACKGROUND: The genomes of laboratory rat strains are characterised by a mosaic haplotype structure caused by their unique breeding history. These mosaic haplotypes have been recently mapped by extensive sequencing of key strains. Comparison of genomic variation between two closely related rat strains with different phenotypes has been proposed as an effective strategy for the discovery of candidate strain-specific regions involved in phenotypic differences. We developed a method to prioritise strain-specific haplotypes by integrating genomic variation and genomic regulatory data predicted to be involved in specific phenotypes...
December 22, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29234104/conjunction-of-potential-g-quadruplex-and-adjacent-cis-elements-in-the-5-utr-of-hepatocyte-nuclear-factor-4-alpha-strongly-inhibit-protein-expression
#8
Shangdong Guo, Hong Lu
Hepatocyte nuclear factor 4-alpha (HNF4α) is a well established master regulator of liver development and function. We identified the in vitro presence of a stable secondary structure, G-quadruplex (G4) in the 5' UTR of P1-HNF4A, the predominant HNF4α isoform(s) in adult liver. Our data suggest that the cooperation of G4 and the adjacent putative protein-binding sites within the 5' UTR was necessary and sufficient to mediate a strong translational repression. This was supported by analysis of deleted/mutated 5'UTRs and two native regulatory single-nucleotide polymorphisms in the 5'UTR...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29216278/systematic-integrative-analysis-of-gene-expression-identifies-hnf4a-as-the-central-gene-in-pathogenesis-of-non-alcoholic-steatohepatitis
#9
Cristina Baciu, Elisa Pasini, Marc Angeli, Katherine Schwenger, Jenifar Afrin, Atul Humar, Sandra Fischer, Keyur Patel, Johane Allard, Mamatha Bhat
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and encompasses a spectrum from simple steatosis to steatohepatitis (NASH). There is currently no approved pharmacologic therapy against NASH, partly due to an incomplete understanding of its molecular basis. The goal of this study was to determine the key differentially expressed genes (DEGs), as well as those genes and pathways central to its pathogenesis. We performed an integrative computational analysis of publicly available gene expression data in NASH from GEO (GSE17470, GSE24807, GSE37031, GSE89632)...
2017: PloS One
https://www.readbyqxmd.com/read/29207974/spectrum-of-mutations-in-monogenic-diabetes-genes-identified-from-high-throughput-dna-sequencing-of-6888-individuals
#10
Vikas Bansal, Johann Gassenhuber, Tierney Phillips, Glenn Oliveira, Rebecca Harbaugh, Nikki Villarasa, Eric J Topol, Thomas Seufferlein, Bernhard O Boehm
BACKGROUND: Diagnosis of monogenic as well as atypical forms of diabetes mellitus has important clinical implications for their specific diagnosis, prognosis, and targeted treatment. Single gene mutations that affect beta-cell function represent 1-2% of all cases of diabetes. However, phenotypic heterogeneity and lack of family history of diabetes can limit the diagnosis of monogenic forms of diabetes. Next-generation sequencing technologies provide an excellent opportunity to screen large numbers of individuals with a diagnosis of diabetes for mutations in disease-associated genes...
December 6, 2017: BMC Medicine
https://www.readbyqxmd.com/read/29194477/regulatory-feedback-loops-bridge-the-human-gene-regulatory-network-and-regulate-carcinogenesis
#11
Yun-Ru Chen, Hsuan-Cheng Huang, Chen-Ching Lin
The development of disease involves a systematic disturbance inside cells and is associated with changes in the interactions or regulations among genes forming biological networks. The bridges inside a network are critical in shortening the distances between nodes. We observed that, inside the human gene regulatory network, one strongly connected core bridged the whole network. Other regulations outside the core formed a weakly connected component surrounding the core like a peripheral structure. Furthermore, the regulatory feedback loops (FBLs) inside the core compose an interface-like structure between the core and periphery...
November 29, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29192290/direct-conversion-of-human-fibroblasts-into-hepatocyte-like-cells-by-atf5-prox1-foxa2-foxa3-and-hnf4a-transduction
#12
Daiki Nakamori, Hiroki Akamine, Kazuo Takayama, Fuminori Sakurai, Hiroyuki Mizuguchi
Recently, it has been reported that human hepatocyte-like cells can be generated from fibroblasts by direct reprogramming technology. However, the conversion efficiency of human induced hepatocyte-like cells (hiHeps) is not high enough. In addition, comparative analysis with the existing models of hepatocytes, such as human iPS cell-derived hepatocyte-like cells and primary human hepatocytes, has not been sufficiently carried out. In this study, we screened hepatic transcription factors for efficient direct hepatic reprogramming and compared hepatic functions between hiHeps and other existing hepatocyte models...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29110545/serum-from-ccl4-induced-acute-rat-injury-model-induces-differentiation-of-adscs-towards-hepatic-cells-and-reduces-liver-fibrosis
#13
Maria Tayyab Baig, Gibran Ali, Sana Javaid Awan, Umara Shehzad, Azra Mehmood, Sadia Mohsin, Shaheen N Khan, Sheikh Riazuddin
Cellular therapies hold promise to alleviate liver diseases. This study explored the potential of allogenic serum isolated from rat with acute CCl4 injury to differentiate adipose derived stem cells (ADSCs) towards hepatic lineage. Acute liver injury was induced by CCl4 which caused significant increase in serum levels of VEGF, SDF1α and EGF. ADSCs were preconditioned with 3% serum isolated from normal and acute liver injury models. ADSCs showed enhanced expression of hepatic markers (AFP, albumin, CK8 and CK19)...
November 7, 2017: Growth Factors
https://www.readbyqxmd.com/read/29093522/genome-wide-discovery-of-long-intergenic-noncoding-rnas-and-their-epigenetic-signatures-in-the-rat
#14
Aimin Li, Zhong-Yin Zhou, Xinhong Hei, Newton O Otecko, Junying Zhang, Yajun Liu, Hongfang Zhou, Zhiqiang Zhao, Lei Wang
Long intergenic noncoding RNAs (lincRNAs) play a crucial role in many biological processes. The rat is an important model organism in biomedical research. Recent studies have detected rat lincRNA genes from several samples. However, identification of rat lincRNAs using large-scale RNA-seq datasets remains unreported. Herein, using more than 100 billion RNA-seq reads from 59 publications together with RefSeq and UniGene annotated RNAs, we report 39,154 lincRNA transcripts encoded by 19,162 lincRNA genes in the rat...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29067470/multiple-micrornas-function-as-self-protective-modules-in-acetaminophen-induced-hepatotoxicity-in-humans
#15
Dianke Yu, Leihong Wu, Pritmohinder Gill, William H Tolleson, Si Chen, Jinchun Sun, Bridgett Knox, Yaqiong Jin, Wenming Xiao, Huixiao Hong, Yong Wang, Zhen Ren, Lei Guo, Nan Mei, Yongli Guo, Xi Yang, Leming Shi, Yinting Chen, Linjuan Zeng, Kostiantyn Dreval, Volodymyr Tryndyak, Igor Pogribny, Hong Fang, Tieliu Shi, Sandra McCullough, Sudeepa Bhattacharyya, Laura Schnackenberg, William Mattes, Richard D Beger, Laura James, Weida Tong, Baitang Ning
Acetaminophen (APAP) overdose is the leading cause of acute liver failure. Yet the mechanisms underlying adaptive tolerance toward APAP-induced liver injury are not fully understood. To better understand molecular mechanisms contributing to adaptive tolerance to APAP is an underpinning foundation for APAP-related precision medicine. In the current study, the mRNA and microRNA (miRNA) expression profiles derived from next generation sequencing data for APAP-treated (5 and 10 mM) HepaRG cells and controls were analyzed systematically...
October 24, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29056335/laser-capture-and-deep-sequencing-reveals-the-transcriptomic-programmes-regulating-the-onset-of-pancreas-and-liver-differentiation-in-human-embryos
#16
Rachel E Jennings, Andrew A Berry, David T Gerrard, Stephen J Wearne, James Strutt, Sarah Withey, Mariya Chhatriwala, Karen Piper Hanley, Ludovic Vallier, Nicoletta Bobola, Neil A Hanley
To interrogate the alternative fates of pancreas and liver in the earliest stages of human organogenesis, we developed laser capture, RNA amplification, and computational analysis of deep sequencing. Pancreas-enriched gene expression was less conserved between human and mouse than for liver. The dorsal pancreatic bud was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored transcription factors. SOX9 and RORA were imputed as key regulators in pancreas compared with EP300, HNF4A, and FOXA family members in liver...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29026101/heterozygous-rfx6-protein-truncating-variants-are-associated-with-mody-with-reduced-penetrance
#17
Kashyap A Patel, Jarno Kettunen, Markku Laakso, Alena Stančáková, Thomas W Laver, Kevin Colclough, Matthew B Johnson, Marc Abramowicz, Leif Groop, Päivi J Miettinen, Maggie H Shepherd, Sarah E Flanagan, Sian Ellard, Nobuya Inagaki, Andrew T Hattersley, Tiinamaija Tuomi, Miriam Cnop, Michael N Weedon
Finding new causes of monogenic diabetes helps understand glycaemic regulation in humans. To find novel genetic causes of maturity-onset diabetes of the young (MODY), we sequenced MODY cases with unknown aetiology and compared variant frequencies to large public databases. From 36 European patients, we identify two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating variants are enriched in the MODY discovery cohort compared to the European control population within ExAC (odds ratio = 131, P = 1 × 10(-4))...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28981576/segtool-a-specifically-expressed-gene-detection-tool-and-applications-in-human-tissue-and-single-cell-sequencing-data
#18
Qiong Zhang, Wei Liu, Chunjie Liu, Sheng-Yan Lin, An-Yuan Guo
Different tissues and diseases have distinct transcriptional profilings with specifically expressed genes (SEGs). So, the identification of SEGs is an important issue in the studies of gene function, biological development, disease mechanism and biomarker discovery. However, few accurate and easy-to-use tools are available for RNA sequencing (RNA-seq) data to detect SEGs. Here, we presented SEGtool, a tool based on fuzzy c-means, Jaccard index and greedy annealing method for SEG detection automatically and self-adaptively ignoring data distribution...
July 7, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28922406/loss-of-liver-specific-and-sexually-dimorphic-gene-expression-by-aryl-hydrocarbon-receptor-activation-in-c57bl-6-mice
#19
Rance Nault, Kelly A Fader, Jack R Harkema, Tim Zacharewski
The aryl hydrocarbon receptor (AhR) is a highly conserved transcription factor that mediates a broad spectrum of species-, strain-, sex-, age-, tissue-, and cell-specific responses elicited by structurally diverse ligands including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dose-dependent effects on liver-specific and sexually dimorphic gene expression were examined in male and female mice gavaged with TCDD every 4 days for 28 or 92 days. RNA-seq data revealed the coordinated repression of 181 genes predominately expressed in the liver including albumin (3...
2017: PloS One
https://www.readbyqxmd.com/read/28885228/genetic-and-transcriptomic-bases-of-intestinal-epithelial-barrier-dysfunction-in-inflammatory-bowel-disease
#20
Maaike Vancamelbeke, Tim Vanuytsel, Ricard Farré, Sare Verstockt, Marc Ferrante, Gert Van Assche, Paul Rutgeerts, Frans Schuit, Séverine Vermeire, Ingrid Arijs, Isabelle Cleynen
BACKGROUND: Intestinal barrier defects are common in patients with inflammatory bowel disease (IBD). To identify which components could underlie these changes, we performed an in-depth analysis of epithelial barrier genes in IBD. METHODS: A set of 128 intestinal barrier genes was selected. Polygenic risk scores were generated based on selected barrier gene variants that were associated with Crohn's disease (CD) or ulcerative colitis (UC) in our study. Gene expression was analyzed using microarray and quantitative reverse transcription polymerase chain reaction...
September 6, 2017: Inflammatory Bowel Diseases
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