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https://www.readbyqxmd.com/read/27909741/the-role-of-epigenetic-modifiers-in-extended-cultures-of-functional-hepatocyte-like-cells-derived-from-human-neonatal-mesenchymal-stem-cells
#1
M Cipriano, J C Correia, S P Camões, N G Oliveira, P Cruz, H Cruz, M Castro, J L Ruas, J M Santos, J P Miranda
The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO)...
December 1, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27902735/role-of-hepatic-specific-transcription-factors-and-polycomb-repressive-complex-2-during-induction-of-fibroblasts-to-hepatic-fate
#2
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Abdulshakour Mohammadnia, Moein Yaqubi
Direct reprogramming using defined sets of transcription factors (TFs) is a recent strategy for generating induced hepatocytes (iHeps) from fibroblasts for use in regenerative medicine and drug development. Comprehensive studies detailing the regulatory role of TFs during this reprogramming process could help increase its efficiency. This study aimed to find the TFs with the greatest influences on the generation of iHeps from fibroblasts, and to further understand their roles in the regulation of the gene expression program...
2016: PloS One
https://www.readbyqxmd.com/read/27899892/age-dependent-hepatic-udp-glucuronosyltransferase-gene-expression-and-activity-in-children
#3
Elizabeth Neumann, Huma Mehboob, Jacqueline Ramírez, Snezana Mirkov, Min Zhang, Wanqing Liu
UDP-glucuronosyltransferases (UGTs) are important phase II drug metabolism enzymes. The aim of this study was to explore the relationship between age and changes in mRNA expression and activity of major human hepatic UGTs, as well as to understand the potential regulatory mechanism underlying this relationship. Using previously generated data, we investigated age-dependent mRNA expression levels of 11 hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17) and 16 transcription factors (AHR, AR, CAR, ESR2, FXR, GCCR, HNF1a, HNF3a, HNF3b, HNF4a, PPARA, PPARG, PPARGC, PXR, SP1, and STAT3) in liver tissue of donors (n = 38) ranging from 0 to 25 years of age...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27889102/analysis-of-gene-expression-and-regulation-implicates-c2h9orf152-has-an-important-role-in-calcium-metabolism-and-chicken-reproduction
#4
Long Liu, Yanfeng Fan, Zhenhe Zhang, Chan Yang, Tuoyu Geng, Daoqing Gong, Zhuocheng Hou, Zhonghua Ning
The reproductive system of a female bird is responsible for egg production. The genes highly expressed in oviduct are potentially important. From RNA-seq analysis, C2H9orf152 (an orthologous gene of human C9orf152) was identified as highly expressed in chicken uterus. To infer its function, we obtained and characterized its complete cDNA sequence, determined its spatiotemporal expression, and probed its transcription factor(s) through pharmaceutical approach. Data showed that the complete cDNA sequence was 1468bp long with a 789bp of open reading frame...
November 11, 2016: Animal Reproduction Science
https://www.readbyqxmd.com/read/27862917/assessing-variation-across-eight-established-east-asian-loci-for-type-2-diabetes-in-american-indians-suggestive-evidence-for-new-sex-specific-diabetes-signals-in-glis3-and-zfand3
#5
Yunhua L Muller, Paolo Piaggi, Peng Chen, Gregory Wiessner, Chidinma Okani, Sayuko Kobes, William C Knowler, Clifton Bogardus, Robert L Hanson, Leslie J Baier
BACKGROUND: Eight new loci for type 2 diabetes (T2D) were identified in an East Asian genome-wide association study meta-analysis. We assess tag SNPs across these loci for associations with T2D in American Indians. METHODS: 435 SNPs which tag (r(2)  ≥ 0.85) common variation across the 8 loci were analyzed for association with T2D (n = 7710), early-onset T2D (n = 1060), body mass index (n = 6839), insulin sensitivity (n = 555) and insulin secretion (n = 298)...
November 8, 2016: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/27836672/transcription-factor-binding-site-enrichment-analysis-predicts-drivers-of-altered-gene-expression-in-nonalcoholic-steatohepatitis
#6
April D Lake, Alexandria L Chaput, Petr Novak, Nathan J Cherrington, Catharine L Smith
The molecular mechanisms behind the transition from simple steatosis to nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD) are not clearly understood. This hinders development of effective therapies for treatment and prevention of NASH. In this study expression profiling data from normal, steatosis, and NASH human livers were used to predict transcription factors that are misregulated as mechanistic features of NAFLD progression. Previously-published human NAFLD gene expression profiling data from normal, steatosis, and NASH livers were subjected to transcription factor binding site enrichment analysis...
December 15, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27829444/potential-molecular-characteristics-in-situ-in-response-to-repetitive-uvb-irradiation
#7
Wenqi Chen, Jinhai Zhang
BACKGROUND: To identify molecular characteristics in situ in response to repetitive UVB (ultraviolet-B) irradiation. METHODS: Microarray data from the Gene Expression Omnibus were re-analyzed to identify DEGs (differentially expressed genes) between UVB-irradiated and non-irradiated skin biopsies. Enrichment and annotation analyses were performed respectively using DAVID, and TSGene and TAG databases. PPIs (protein-protein interactions) were analyzed using STRING, and miRNAs (microRNAs) and TFs (transcription factors) were predicted separately by miRNA-related databases and ENCODE...
November 10, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27820600/direct-reprogramming-of-fibroblasts-into-renal-tubular-epithelial-cells-by-defined-transcription-factors
#8
Michael M Kaminski, Jelena Tosic, Catena Kresbach, Hannes Engel, Jonas Klockenbusch, Anna-Lena Müller, Roman Pichler, Florian Grahammer, Oliver Kretz, Tobias B Huber, Gerd Walz, Sebastian J Arnold, Soeren S Lienkamp
Direct reprogramming by forced expression of transcription factors can convert one cell type into another. Thus, desired cell types can be generated bypassing pluripotency. However, direct reprogramming towards renal cells remains an unmet challenge. Here, we identify renal cell fate-inducing factors on the basis of their tissue specificity and evolutionarily conserved expression, and demonstrate that combined expression of Emx2, Hnf1b, Hnf4a and Pax8 converts mouse and human fibroblasts into induced renal tubular epithelial cells (iRECs)...
November 7, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27810688/clinical-whole-exome-sequencing-in-early-onset-diabetes-patients
#9
Soo Heon Kwak, Chan-Hyeon Jung, Chang Ho Ahn, Jungsun Park, Jeesoo Chae, Hye Seung Jung, Young Min Cho, Dae Ho Lee, Jong-Il Kim, Kyong Soo Park
AIMS: There could be an overlap of monogenic diabetes and early onset type 2 diabetes in those who are diagnosed before age of 30years. Genetic diagnosis in these patients might improve the quality of care. A limited number of studies have used whole exome sequencing (WES) in Asian patients with early onset diabetes, and the clinical utility of WES is largely unknown. METHODS: We performed whole exome capture and massive parallel sequencing in 28 patients with early onset diabetes...
October 15, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27790929/allele-and-genotype-frequencies-of-genes-relevant-to-anti-epileptic-drug-therapy-in-mexican-mestizo-healthy-volunteers
#10
Ingrid Fricke-Galindo, Alberto Ortega-Vázquez, Nancy Monroy-Jaramillo, Pedro Dorado, Helgi Jung-Cook, Eva Peñas-Lledó, Adrián LLerena, Marisol López-López
AIM: To determine allele and genotype frequencies of genes influencing anti-epileptic drug therapy in Mexican-Mestizo (MM) healthy volunteers, and to evaluate whether these are different from those reported for other populations. SUBJECTS & METHODS: Thirty-nine variants of CYP3A5, EPHX1, NR1I2, HNF4A, UGT1A1, UGT2B7, ABCC2, RALBP1, SCN1A, SCN2A and GABRA1 were genotyped in 300 MM healthy volunteers. RESULTS: All studied alleles were presented in MM, except for seven UGT1A1 variants (*6-8, 14, 15, 27 and 29)...
October 28, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27752141/diabetes-linked-transcription-factor-hnf4%C3%AE-regulates-metabolism-of-endogenous-methylarginines-and-%C3%AE-aminoisobutyric-acid-by-controlling-expression-of-alanine-glyoxylate-aminotransferase-2
#11
Dmitry V Burdin, Alexey A Kolobov, Chad Brocker, Alexey A Soshnev, Nikolay Samusik, Anton V Demyanov, Silke Brilloff, Natalia Jarzebska, Jens Martens-Lobenhoffer, Maren Mieth, Renke Maas, Stefan R Bornstein, Stefanie M Bode-Böger, Frank Gonzalez, Norbert Weiss, Roman N Rodionov
Elevated levels of circulating asymmetric and symmetric dimethylarginines (ADMA and SDMA) predict and potentially contribute to end organ damage in cardiovascular diseases. Alanine-glyoxylate aminotransferase 2 (AGXT2) regulates systemic levels of ADMA and SDMA, and also of beta-aminoisobutyric acid (BAIB)-a modulator of lipid metabolism. We identified a putative binding site for hepatic nuclear factor 4 α (HNF4α) in AGXT2 promoter sequence. In a luciferase reporter assay we found a 75% decrease in activity of Agxt2 core promoter after disruption of the HNF4α binding site...
October 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27727071/developmental-regulation-of-cyp3a4-and-cyp3a7-in-chinese-han-population
#12
Hang He, Ya-Li Nie, Jiang-Feng Li, Xiang-Guang Meng, Wei-Hong Yang, Yu-Long Chen, Shu-Jie Wang, Xiaochao Ma, Quan-Cheng Kan, Li-Rong Zhang
CYP3A4 and CYP3A7 are generally served as the major adult and fetal liver forms, respectively, and exhibited a developmental switch during liver maturation. The objective of this study was to explore the potential mechanisms associated with the developmental switch of CYP3A4 and CYP3A7 in the Chinese Han population. We analyzed CYP3A4/7, nuclear receptors, and epigenetic modifications in human liver samples. We found that the expression levels of CYP3A4 mRNA in adults were significantly higher than the levels in fetus...
September 9, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27721404/a-pre-neoplastic-epigenetic-field-defect-in-hcv-infected-liver-at-transcription-factor-binding-sites-and-polycomb-targets
#13
N A Wijetunga, M Pascual, J Tozour, F Delahaye, M Alani, M Adeyeye, A W Wolkoff, A Verma, J M Greally
The predisposition of patients with Hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) involves components of viral infection, inflammation and time. The development of multifocal, genetically distinct tumours is suggestive of a field defect affecting the entire liver. The molecular susceptibility mediating such a field defect is not understood. One potential mediator of long-term cellular reprogramming is heritable (epigenetic) regulation of transcription, exemplified by DNA methylation. We studied epigenetic and transcriptional changes in HCV-infected livers in comparison with control, uninfected livers and HCC, allowing us to identify pre-neoplastic epigenetic and transcriptional events...
October 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27704169/hepatic-expression-of-transcription-factors-affecting-developmental-regulation-of-ugt1a1-in-the-han-chinese-population
#14
Ya-Li Nie, Hang He, Jiang-Feng Li, Xiang-Guang Meng, Liang Yan, Pei Wang, Shu-Jie Wang, Hong-Zheng Bi, Li-Rong Zhang, Quan-Cheng Kan
PURPOSE: Complete or partial inactivity of UGT1A1, the unique enzyme responsible for bilirubin glucuronidation, is commonly associated with hyperbilirubinemia. We investigated the dynamic expression of UGT1A1, and that of the transcription factors (TFs) involved in its developmental regulation, during human hepatic growth in Han Chinese individuals. METHODS: Eighty-eight prenatal, pediatric, and adult liver samples were obtained from Han Chinese individuals. Quantitative real-time polymerase chain reaction was used to evaluate mRNA expression of UGT1A1 and TFs including PXR, CAR, HNF1A, HNF4A, PPARA, etc...
October 5, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27698357/impact-of-high-fat-diet-on-long-non-coding-rnas-and-messenger-rnas-expression-in-the-aortas-of-apoe-mice
#15
Mei-Hua Bao, Huai-Qing Luo, Li-Hua Chen, Liang Tang, Kui-Fen Ma, Ju Xiang, Li-Ping Dong, Jie Zeng, Guang-Yi Li, Jian-Ming Li
Atherosclerosis is a chronic multifactorial inflammatory disease with high prevalence worldwide, and has become the leading cause of death. The present study was designed to investigate the impact of high-fat diet on ApoE(-/-) mice exhibiting atherosclerosis by detecting the genome-wide expression profile of lncRNAs and mRNAs. A total of 354 differentially expressed lncRNAs were identified (≥2.0 folds). Simultaneously, 357 differentially expressed mRNAs from the same chip were found. The expression differences of lncRNAs and mRNAs were consistent in both qPCR and microarray detection...
October 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27610270/hepatic-differentiation-of-human-induced-pluripotent-stem-cells-in-a-perfused-three-dimensional-multicompartment-bioreactor
#16
Nora Freyer, Fanny Knöspel, Nadja Strahl, Leila Amini, Petra Schrade, Sebastian Bachmann, Georg Damm, Daniel Seehofer, Frank Jacobs, Mario Monshouwer, Katrin Zeilinger
The hepatic differentiation of human induced pluripotent stem cells (hiPSC) holds great potential for application in regenerative medicine, pharmacological drug screening, and toxicity testing. However, full maturation of hiPSC into functional hepatocytes has not yet been achieved. In this study, we investigated the potential of a dynamic three-dimensional (3D) hollow fiber membrane bioreactor technology to improve the hepatic differentiation of hiPSC in comparison to static two-dimensional (2D) cultures. A total of 100 × 10(6) hiPSC were seeded into each 3D bioreactor (n = 3)...
2016: BioResearch Open Access
https://www.readbyqxmd.com/read/27583195/claudin-based-barrier-differentiation-in-the-colonic-epithelial-crypt-niche-involves-hopx-klf4-and-tcf7l2-hnf4-%C3%AE-cascades
#17
Loukia N Lili, Attila E Farkas, Christian Gerner-Smidt, Christian E Overgaard, Carlos S Moreno, Charles A Parkos, Christopher T Capaldo, Asma Nusrat
Colonic enterocytes form a rapidly renewing epithelium and barrier to luminal antigens. During renewal, coordinated expression of the claudin family of genes is vital to maintain the epithelial barrier. Disruption of this process contributes to barrier compromise and mucosal inflammatory diseases. However, little is known about the regulation of this critical aspect of epithelial cell differentiation. In order to identify claudin regulatory factors we utilized high-throughput gene microarrays and correlation analyses...
July 2016: Tissue Barriers
https://www.readbyqxmd.com/read/27571483/the-genetic-architecture-of-diabetes-in-pregnancy-implications-for-clinical-practice
#18
Jeffrey W Kleinberger, Kristin A Maloney, Toni I Pollin
The genetic architecture of diabetes mellitus in general and in pregnancy is complex, owing to the multiple types of diabetes that comprise both complex/polygenic forms and monogenic (largely caused by a mutation in a single gene) forms such as maturity-onset diabetes of the young (MODY). Type 1 diabetes (T1D) and type 2 diabetes (T2D) have complex genetic etiologies, with over 40 and 90 genes/loci, respectively, implicated that interact with environmental/lifestyle factors. The genetic etiology of gestational diabetes mellitus has largely been found to overlap that of T2D...
August 29, 2016: American Journal of Perinatology
https://www.readbyqxmd.com/read/27569862/differentiation-of-human-foreskin-fibroblast-derived-induced-pluripotent-stem-cells-into-hepatocyte-like-cells
#19
Jianjun Wang, Ping Zhao, Zhihong Wan, Xueyuan Jin, Yongqian Cheng, Tao Yan, Song Qing, Ning Ding, Shaojie Xin
: The aim of this study was to investigate the differentiation potential of induced pluripotent stem cells (iPSCs) derived from human foreskin fibroblasts (HFFs) into hepatocyte-like cells (HLCs). The iPSCs were firstly induced by transduction of OCT4, SOX2, KLF4, and c-MYC into HFFs using retrovirus. Afterwards, expressions of pluripotency factors were identified by semiquantitative reverse transcription-polymerase chain reaction and immunofluorescence staining, and karyotype, embryoid, and teratoma were observed by microscope...
October 2016: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27552834/prolonged-episodes-of-hypoglycaemia-in-hnf4a-mody-mutation-carriers-with-igt-evidence-of-persistent-hyperinsulinism-into-early-adulthood
#20
S Bacon, M P Kyithar, E M Condron, N Vizzard, M Burke, M M Byrne
AIMS: HNF4A is an established cause of maturity onset diabetes of the young (MODY). Congenital hyperinsulinism can also be associated with mutations in the HNF4A gene. A dual phenotype is observed in HNF4A-MODY with hyperinsulinaemic hypoglycaemia in the neonatal period progressing to diabetes in adulthood. The nature and timing of the transition remain poorly defined. We performed an observational study to establish changes in glycaemia and insulin secretion over a 6-year period. We investigated glycaemic variability and hypoglycaemia in HNF4A-MODY using a continuous glucose monitoring system (CGMS)...
August 23, 2016: Acta Diabetologica
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