{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:04:09Z","timestamp":1790370249086,"version":"4.1.0"},"reference-count":162,"publisher":"Elsevier BV","issue":"1-2","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017559","name":"Recordati Rare Diseases Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017559","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Genetics and Metabolism"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.ymgme.2026.110241","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T23:39:04Z","timestamp":1787269144000},"page":"110241","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human cell-based models for urea cycle research: From gene regulation and ureagenesis to disease modeling and therapeutic development"],"prefix":"10.1016","volume":"149","author":[{"given":"Ljubica","family":"Caldovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymgme.2026.110241_bb0005","series-title":"The Liver: Biology and Pathobiology","first-page":"1","article-title":"Organizational principles of the liver","author":"Nagy","year":"2020"},{"key":"10.1016\/j.ymgme.2026.110241_bb0010","series-title":"The Metabolic & Molecular Bases of Inherited Disease","first-page":"1909","article-title":"Urea cycle enzymes","author":"Brusilow","year":"2001"},{"key":"10.1016\/j.ymgme.2026.110241_bb0015","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1042\/bj20030002","article-title":"N-acetylglutamate and its changing role through evolution","volume":"372","author":"Caldovic","year":"2003","journal-title":"Biochem. J."},{"key":"10.1016\/j.ymgme.2026.110241_bb0020","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1152\/physrev.1990.70.3.701","article-title":"Nitrogen metabolism and ornithine cycle function","volume":"70","author":"Meijer","year":"1990","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ymgme.2026.110241_bb0025","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0076-6879(85)13007-7","article-title":"N-Acetylglutamate synthase","volume":"113","author":"Powers-Lee","year":"1985","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0030","series-title":"Inborn Errors of Metabolism: From Neonatal Screening to Metabolic Pathways","article-title":"Urea cycle: ureagenesis and non-ureagenic functions","author":"Shchelochkov","year":"2014"},{"key":"10.1016\/j.ymgme.2026.110241_bb0035","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00281-025-01038-9","article-title":"Arginine metabolism in myeloid cells in health and disease","volume":"47","author":"Karadima","year":"2025","journal-title":"Semin. Immunopathol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0040","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1007\/s00109-021-02123-w","article-title":"Immunosuppressive network promotes immunosenescence associated with aging and chronic inflammatory conditions","volume":"99","author":"Salminen","year":"2021","journal-title":"J. Mol. Med. (Berl.)"},{"key":"10.1016\/j.ymgme.2026.110241_bb0045","doi-asserted-by":"crossref","DOI":"10.1124\/pharmrev.124.001271","article-title":"Biochemistry, pharmacology, and in vivo function of arginases","volume":"77","author":"Heuser","year":"2025","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.ymgme.2026.110241_bb0050","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s40272-025-00719-0","article-title":"Current treatment modalities for urea cycle disorders","volume":"27","author":"Ah Mew","year":"2025","journal-title":"Paediatr. Drugs"},{"key":"10.1016\/j.ymgme.2026.110241_bb0055","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/jimd.12100","article-title":"Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision","volume":"42","author":"Haberle","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2026.110241_bb0060","series-title":"Safety, Tolerability and Pharmacokinetics of ARCT-810 in Healthy Adult Subjects","author":"NCT06488313","year":"2023"},{"key":"10.1016\/j.ymgme.2026.110241_bb0065","series-title":"Phase 1b Study to Assess Safety, Tolerability, and Pharmacokinetics of ARCT-810 in Stable Adult Subjects With Ornithine Transcarbamylase Deficiency","author":"NCT04416126","year":"2024"},{"key":"10.1016\/j.ymgme.2026.110241_bb0070","series-title":"An Open-label Study to Investigate ECUR-506 in Male Babies Less Than 9 Months of Age With Neonatal Onset OTC Deficiency","author":"NCT06255782","year":"2026"},{"key":"10.1016\/j.ymgme.2026.110241_bb0075","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1056\/NEJMoa2504747","article-title":"Patient-specific in vivo gene editing to treat a rare genetic disease","volume":"392","author":"Musunuru","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymgme.2026.110241_bb0080","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/hep.20764","article-title":"The modular microarchitecture of human liver","volume":"42","author":"Teutsch","year":"2005","journal-title":"Hepatology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0085","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/0026-2862(73)90021-6","article-title":"The microcirculatory hepatic unit","volume":"6","author":"Rappaport","year":"1973","journal-title":"Microvasc. Res."},{"key":"10.1016\/j.ymgme.2026.110241_bb0090","series-title":"The Liver: Biology and Pathobiology","first-page":"36","article-title":"Hepatocyte surface polarity","author":"M\u00fcsch","year":"2020"},{"key":"10.1016\/j.ymgme.2026.110241_bb0095","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1152\/physrev.1989.69.3.708","article-title":"Functional specialization of different hepatocyte populations","volume":"69","author":"Jungermann","year":"1989","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ymgme.2026.110241_bb0100","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1002\/hep.22537","article-title":"Liver-specific ablation of integrin-linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly","volume":"48","author":"Gkretsi","year":"2008","journal-title":"Hepatology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0105","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1432-1033.1979.tb13082.x","article-title":"Permissive effect of dexamethasone on glucagon induction of urea-cycle enzymes in perifused primary monolayer cultures of rat hepatocytes","volume":"97","author":"Gebhardt","year":"1979","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.ymgme.2026.110241_bb0110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj1860001","article-title":"Inhibition of urea-cycle activity by high concentrations of alanine","volume":"186","author":"Hensgens","year":"1980","journal-title":"Biochem. J."},{"key":"10.1016\/j.ymgme.2026.110241_bb0115","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0167-4781(83)90008-8","article-title":"Effects of glucagon on biosynthesis of the mitochondrial enzyme, carbamoyl-phosphate synthase I, in primary hepatocytes and Morris hepatoma 5123D","volume":"741","author":"Rozen","year":"1983","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymgme.2026.110241_bb0120","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/bj2160281","article-title":"Hormonal regulation of two urea-cycle enzymes in cultured foetal hepatocytes","volume":"216","author":"Husson","year":"1983","journal-title":"Biochem. J."},{"key":"10.1016\/j.ymgme.2026.110241_bb0125","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1210\/endo-119-3-1171","article-title":"Effects of pancreatic hormones and glucocorticosteroids on argininosuccinate synthetase and argininosuccinase activities of rat liver during the perinatal period: in vivo and in vitro studies","volume":"119","author":"Husson","year":"1986","journal-title":"Endocrinology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0130","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1620\/tjem.158.309","article-title":"The role of amino acids and their transport systems in the regulation of ureogenesis in the primary culture of adult rat hepatocytes","volume":"158","author":"Nagao","year":"1989","journal-title":"Tohoku J. Exp. Med."},{"key":"10.1016\/j.ymgme.2026.110241_bb0135","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/0006-2952(91)90328-3","article-title":"On the mechanism of inhibition of gluconeogenesis and ureagenesis by sodium benzoate","volume":"42","author":"Cyr","year":"1991","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0140","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1432-1033.1996.00056.x","article-title":"Glutamine increases argininosuccinate synthetase mRNA levels in rat hepatocytes. The involvement of cell swelling","volume":"236","author":"Quillard","year":"1996","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.ymgme.2026.110241_bb0145","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/0006-291X(75)90380-0","article-title":"Primary culture of normal adult rat liver cells which maintain stable urea cycle enzymes","volume":"64","author":"Lin","year":"1975","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ymgme.2026.110241_bb0150","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1016\/S0021-9258(17)40885-4","article-title":"Induction of urea cycle enzymes of rat liver by glucagon","volume":"253","author":"Snodgrass","year":"1978","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2026.110241_bb0155","doi-asserted-by":"crossref","first-page":"5061","DOI":"10.1016\/S0021-9258(18)34635-0","article-title":"Induction of urea cycle enzymes by glucagon and dexamethasone in monolayer cultures of adult rat hepatocytes","volume":"257","author":"Lin","year":"1982","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2026.110241_bb0160","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1006\/abbi.1993.1139","article-title":"Coordinate induction of the urea cycle enzymes by glucagon and dexamethasone is accomplished by three different mechanisms","volume":"301","author":"Ulbright","year":"1993","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.ymgme.2026.110241_bb0165","author":"NIH to Prioritize Human-Based Research Technologies"},{"key":"10.1016\/j.ymgme.2026.110241_bb0170","doi-asserted-by":"crossref","DOI":"10.1002\/jimd.70021","article-title":"Current understanding of pathogenic mechanisms and disease models of Citrin deficiency","volume":"48","author":"Lacabanne","year":"2025","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2026.110241_bb0175","article-title":"Functional characterization of the spf\/ash splicing variation in OTC deficiency of mice and man","volume":"10","author":"Rivera-Barahona","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.ymgme.2026.110241_bb0180","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/s00109-015-1354-3","article-title":"Arginase-1 deficiency","volume":"93","author":"Sin","year":"2015","journal-title":"J. Mol. Med. (Berl.)"},{"key":"10.1016\/j.ymgme.2026.110241_bb0185","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.cca.2016.11.038","article-title":"A simple dried blood spot-method for in vivo measurement of ureagenesis by gas chromatography-mass spectrometry using stable isotopes","volume":"464","author":"Allegri","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"10.1016\/j.ymgme.2026.110241_bb0190","doi-asserted-by":"crossref","first-page":"629","DOI":"10.2174\/138920006778017759","article-title":"Molecular mechanisms underlying the dedifferentiation process of isolated hepatocytes and their cultures","volume":"7","author":"Elaut","year":"2006","journal-title":"Curr. Drug Metab."},{"key":"10.1016\/j.ymgme.2026.110241_bb0195","doi-asserted-by":"crossref","DOI":"10.1016\/j.xpro.2023.102391","article-title":"Isolation of primary human liver cells from normal and nonalcoholic steatohepatitis livers","volume":"4","author":"Liu","year":"2023","journal-title":"STAR Protoc."},{"key":"10.1016\/j.ymgme.2026.110241_bb0200","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/0309-1651(82)90187-4","article-title":"High yield preparation of isolated human adult hepatocytes by enzymatic perfusion of the liver","volume":"6","author":"Guguen-Guillouzo","year":"1982","journal-title":"Cell Biol. Int. Rep."},{"key":"10.1016\/j.ymgme.2026.110241_bb0205","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1002\/hep.22880","article-title":"Extracellular matrix modulates sensitivity of hepatocytes to fibroblastoid dedifferentiation and transforming growth factor beta-induced apoptosis","volume":"49","author":"Godoy","year":"2009","journal-title":"Hepatology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0210","article-title":"Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture","volume":"7","author":"Guo","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymgme.2026.110241_bb0215","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1124\/dmd.105.007708","article-title":"Gene expression in human hepatocytes in suspension after isolation is similar to the liver of origin, is not affected by hepatocyte cold storage and cryopreservation, but is strongly changed after hepatocyte plating","volume":"34","author":"Richert","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ymgme.2026.110241_bb0220","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1021\/bp000099d","article-title":"Ammonia removal using hepatoma cells in mammalian cell cultures","volume":"16","author":"Choi","year":"2000","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.ymgme.2026.110241_bb0225","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1002\/hep.28780","article-title":"Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation","volume":"64","author":"Lauschke","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0230","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0300-483X(93)02611-J","article-title":"Rat hepatocyte cultures and co-cultures in biotransformation studies of xenobiotics","volume":"82","author":"Rogiers","year":"1993","journal-title":"Toxicology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0235","doi-asserted-by":"crossref","DOI":"10.1016\/j.ygeno.2022.110330","article-title":"Rapid changes in chromatin structure during dedifferentiation of primary hepatocytes in vitro","volume":"114","author":"Seirup","year":"2022","journal-title":"Genomics"},{"key":"10.1016\/j.ymgme.2026.110241_bb0240","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/liv.12577","article-title":"Molecular mechanisms controlling the phenotype and the EMT\/MET dynamics of hepatocyte","volume":"35","author":"Cicchini","year":"2015","journal-title":"Liver Int."},{"key":"10.1016\/j.ymgme.2026.110241_bb0245","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1126\/science.aau7307","article-title":"Long-term functional maintenance of primary human hepatocytes in vitro","volume":"364","author":"Xiang","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.ymgme.2026.110241_bb0250","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/S0006-2952(02)01382-5","article-title":"Influence of isolation procedure, extracellular matrix and dexamethasone on the regulation of membrane transporters gene expression in rat hepatocytes","volume":"64","author":"Luttringer","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0255","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1248\/bpb.b24-00180","article-title":"Suppression of the epithelial-mesenchymal transition and maintenance of the liver functions in primary hepatocytes through dispersion culture within a dome-shaped collagen matrix","volume":"47","author":"Tonooka","year":"2024","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.ymgme.2026.110241_bb0260","doi-asserted-by":"crossref","DOI":"10.1186\/s13062-026-00755-x","article-title":"The impact of mesenchymal stromal cells on the proliferation and functional maturation of liver organoids","volume":"21","author":"Luo","year":"2026","journal-title":"Biol. Direct"},{"key":"10.1016\/j.ymgme.2026.110241_bb0265","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s004410100429","article-title":"Regulation of cell morphology and cytochrome P450 expression in human hepatocytes by extracellular matrix and cell-cell interactions","volume":"306","author":"Hamilton","year":"2001","journal-title":"Cell Tissue Res."},{"key":"10.1016\/j.ymgme.2026.110241_bb0270","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S0006-2952(97)00204-9","article-title":"Drug metabolism in hepatocyte sandwich cultures of rats and humans","volume":"54","author":"Kern","year":"1997","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0275","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s11626-997-0065-7","article-title":"Extended primary culture of human hepatocytes in a collagen gel sandwich system","volume":"33","author":"Kono","year":"1997","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"10.1016\/j.ymgme.2026.110241_bb0280","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-33332-9","article-title":"Expression and function of CYP enzymes and hepatobiliary transporters in an improved long-term sandwich culture hepatocyte model","volume":"16","author":"Pacsuta","year":"2026","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymgme.2026.110241_bb0285","doi-asserted-by":"crossref","DOI":"10.1016\/j.mex.2020.101080","article-title":"Drug-induced cholestasis assay in primary hepatocytes","volume":"7","author":"Van Brantegem","year":"2020","journal-title":"MethodsX"},{"key":"10.1016\/j.ymgme.2026.110241_bb0290","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/toxsci\/kfx289","article-title":"Comparison of hepatic 2D Sandwich cultures and 3D spheroids for long-term toxicity applications: a multicenter study","volume":"162","author":"Bell","year":"2018","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.ymgme.2026.110241_bb0295","doi-asserted-by":"crossref","DOI":"10.1038\/srep25187","article-title":"Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease","volume":"6","author":"Bell","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymgme.2026.110241_bb0300","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1124\/dmd.116.074369","article-title":"Transcriptional, functional, and mechanistic comparisons of stem cell-derived hepatocytes, HepaRG cells, and three-dimensional human hepatocyte spheroids as predictive in vitro systems for drug-induced liver injury","volume":"45","author":"Bell","year":"2017","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ymgme.2026.110241_bb0305","doi-asserted-by":"crossref","DOI":"10.1088\/1758-5090\/ac7825","article-title":"In vitrolong term differentiation and functionality of three-dimensional bioprinted primary human hepatocytes: application forin vivoengraftment","volume":"14","author":"Cuvellier","year":"2022","journal-title":"Biofabrication"},{"key":"10.1016\/j.ymgme.2026.110241_bb0310","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1002\/cpt.2887","article-title":"3D spheroid primary human hepatocytes for prediction of cytochrome P450 and drug transporter induction","volume":"113","author":"Jarvinen","year":"2023","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.ymgme.2026.110241_bb0315","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.xphs.2020.10.043","article-title":"Primary human hepatocyte spheroid model as a 3D in vitro platform for metabolism studies","volume":"110","author":"Kanebratt","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ymgme.2026.110241_bb0320","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1096\/fj.201601375R","article-title":"Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics","volume":"31","author":"Vorrink","year":"2017","journal-title":"FASEB J."},{"key":"10.1016\/j.ymgme.2026.110241_bb0325","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.dmpk.2019.11.002","article-title":"Establishment of a primary human hepatocyte spheroid system for evaluating metabolic toxicity using dacarbazine under conditions of CYP1A2 induction","volume":"35","author":"Mizoi","year":"2020","journal-title":"Drug Metab. Pharmacokinet."},{"key":"10.1016\/j.ymgme.2026.110241_bb0330","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/s41598-020-80019-4","article-title":"Generation of proliferating human adult hepatocytes using optimized 3D culture conditions","volume":"11","author":"Rose","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymgme.2026.110241_bb0335","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/j.cell.2018.11.013","article-title":"Long-term expansion of functional mouse and human hepatocytes as 3D organoids","volume":"175","author":"Hu","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.ymgme.2026.110241_bb0340","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1089\/scd.2019.0064","article-title":"Guide to the assessment of mature liver gene expression in stem cell-derived hepatocytes","volume":"28","author":"Zabulica","year":"2019","journal-title":"Stem Cells Dev."},{"key":"10.1016\/j.ymgme.2026.110241_bb0345","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/s41586-025-08861-y","article-title":"Generation of human adult hepatocyte organoids with metabolic functions","volume":"641","author":"Igarashi","year":"2025","journal-title":"Nature"},{"key":"10.1016\/j.ymgme.2026.110241_bb0350","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nmeth.1591","article-title":"A more efficient method to generate integration-free human iPS cells","volume":"8","author":"Okita","year":"2011","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymgme.2026.110241_bb0355","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.ymgme.2026.110241_bb0360","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/hep.24790","article-title":"Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol","volume":"55","author":"Chen","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0365","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/hep.23354","article-title":"Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells","volume":"51","author":"Si-Tayeb","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0370","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1038\/cr.2009.107","article-title":"Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells","volume":"19","author":"Song","year":"2009","journal-title":"Cell Res."},{"key":"10.1016\/j.ymgme.2026.110241_bb0375","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1002\/hep.21582","article-title":"Directed differentiation of human embryonic stem cells into functional hepatic cells","volume":"45","author":"Cai","year":"2007","journal-title":"Hepatology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0380","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/jcp.24501","article-title":"Direct differentiation of homogeneous human adipose stem cells into functional hepatocytes by mimicking liver embryogenesis","volume":"229","author":"Li","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0385","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1089\/scd.2015.0342","article-title":"Malfunction in mitochondrial beta-oxidation contributes to lipid accumulation in hepatocyte-like cells derived from Citrin deficiency-induced pluripotent stem cells","volume":"25","author":"Kim","year":"2016","journal-title":"Stem Cells Dev."},{"key":"10.1016\/j.ymgme.2026.110241_bb0390","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.bbrc.2017.03.037","article-title":"Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs","volume":"486","author":"Yoshitoshi-Uebayashi","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ymgme.2026.110241_bb0395","series-title":"Ultragenyx Announces Positive 36-Week Data from Phase 3 Study of DTX301 AAV8 Gene Therapy for the Treatment of Ornithine Transcarbamylase (OTC) Deficiency","author":"Higa","year":"2026"},{"key":"10.1016\/j.ymgme.2026.110241_bb0400","doi-asserted-by":"crossref","first-page":"e394","DOI":"10.1038\/mtna.2016.98","article-title":"Restoring ureagenesis in hepatocytes by CRISPR\/Cas9-mediated genomic addition to arginase-deficient induced pluripotent stem cells","volume":"5","author":"Lee","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.ymgme.2026.110241_bb0405","first-page":"545","article-title":"CRISPR-mediated genomic addition to CPS1 deficient iPSCs is insufficient to restore nitrogen homeostasis","volume":"94","author":"Nitzahn","year":"2021","journal-title":"Yale J. Biol. Med."},{"key":"10.1016\/j.ymgme.2026.110241_bb0410","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The genotype-tissue expression (GTEx) project","volume":"45","author":"G.T. Consortium","year":"2013","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ymgme.2026.110241_bb0415","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nature24277","article-title":"Genetic effects on gene expression across human tissues","volume":"550","author":"G.T. Consortium","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.ymgme.2026.110241_bb0420","doi-asserted-by":"crossref","DOI":"10.1016\/j.ymthe.2026.06.044","article-title":"Functional editing of the OTC locus by targeted integration with phenotype correction and restoration of endogenous expression patterns","author":"Ginn","year":"2026","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymgme.2026.110241_bb0425","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aba3312","article-title":"Restoring the natural tropism of AAV2 vectors for human liver","volume":"12","author":"Cabanes-Creus","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymgme.2026.110241_bb0430","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1089\/hum.2019.264","article-title":"High-throughput in vitro, ex vivo, and in vivo screen of adeno-associated virus vectors based on physical and functional transduction","volume":"31","author":"Westhaus","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymgme.2026.110241_bb0435","article-title":"Diagnostic challenges in ornithine transcarbamylase deficiency lacking genetic confirmation: liver biopsy versus human induced pluripotent stem cell technology","volume":"44","author":"Laemmle","year":"2025","journal-title":"Mol. Genet. Metab. Rep."},{"key":"10.1016\/j.ymgme.2026.110241_bb0440","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/hep.32247","article-title":"Aquaporin 9 induction in human iPSC-derived hepatocytes facilitates modeling of ornithine transcarbamylase deficiency","volume":"76","author":"Laemmle","year":"2022","journal-title":"Hepatology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0445","doi-asserted-by":"crossref","first-page":"937","DOI":"10.2169\/internalmedicine.1851-18","article-title":"Hyperammonemia in a woman with late-onset ornithine transcarbamylase deficiency","volume":"58","author":"Koya","year":"2019","journal-title":"Intern. Med."},{"key":"10.1016\/j.ymgme.2026.110241_bb0450","doi-asserted-by":"crossref","DOI":"10.1002\/jimd.70043","article-title":"Novel treatment strategy for patients with urea cycle disorders: pharmacological chaperones enhance enzyme stability and activity in patient-derived liver disease models","volume":"48","author":"Ramosaj","year":"2025","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2026.110241_bb0455","doi-asserted-by":"crossref","DOI":"10.1093\/toxsci\/kfaf171","article-title":"Computational integration of in vivo single cell and in vitro bulk transcriptomics across 236 human and mouse datasets differentiates physiological versus non-physiological hepatic cell lines for hepatotoxicity screening","volume":"209","author":"Kowal","year":"2026","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.ymgme.2026.110241_bb0460","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/toxsci\/kfy084","article-title":"Proteomic comparison of various hepatic cell cultures for preclinical safety pharmacology","volume":"164","author":"Hurrell","year":"2018","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.ymgme.2026.110241_bb0465","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.stemcr.2019.08.007","article-title":"Robust, long-term culture of endoderm-derived hepatic organoids for disease modeling","volume":"13","author":"Akbari","year":"2019","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.ymgme.2026.110241_bb0470","article-title":"Modeling alcohol-associated liver disease in humans using adipose stromal or stem cell-derived organoids","volume":"4","author":"Bi","year":"2024","journal-title":"Cell Rep. Methods"},{"key":"10.1016\/j.ymgme.2026.110241_bb0475","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature12271","article-title":"Vascularized and functional human liver from an iPSC-derived organ bud transplant","volume":"499","author":"Takebe","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.ymgme.2026.110241_bb0480","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.jhep.2018.12.028","article-title":"Generation of hepatobiliary organoids from human induced pluripotent stem cells","volume":"70","author":"Wu","year":"2019","journal-title":"J. Hepatol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0485","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1038\/nprot.2016.097","article-title":"Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation","volume":"11","author":"Broutier","year":"2016","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.ymgme.2026.110241_bb0490","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cell.2014.11.050","article-title":"Long-term culture of genome-stable bipotent stem cells from adult human liver","volume":"160","author":"Huch","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.ymgme.2026.110241_bb0495","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ymgme.2021.04.001","article-title":"Biomarkers for liver disease in urea cycle disorders","volume":"133","author":"Nagamani","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2026.110241_bb0500","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ymgme.2014.08.001","article-title":"A longitudinal study of urea cycle disorders","volume":"113","author":"Batshaw","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2026.110241_bb0505","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s10545-017-0088-5","article-title":"Liver involvement in urea cycle disorders: a review of the literature","volume":"40","author":"Bigot","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2026.110241_bb0510","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1038\/s41598-025-32539-0","article-title":"Temporal proteomic profiling of iPSC-derived human liver organoids reveals optimal maturation for drug metabolism and toxicology","volume":"16","author":"Yang","year":"2026","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymgme.2026.110241_bb0515","doi-asserted-by":"crossref","DOI":"10.1007\/s10565-026-10203-1","article-title":"Improving hepatic metabolic function with 3D iPSC-derived human hepatocytes","volume":"42","author":"Pozo Garcia","year":"2026","journal-title":"Cell Biol. Toxicol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0520","doi-asserted-by":"crossref","DOI":"10.1177\/19373341261419502","article-title":"Generation of 3D liver microtissues from induced pluripotent stem cells","author":"Han","year":"2026","journal-title":"Tissue Eng. Part A"},{"key":"10.1016\/j.ymgme.2026.110241_bb0525","doi-asserted-by":"crossref","first-page":"3380","DOI":"10.1039\/c0lc00135j","article-title":"Perfusion-based microfluidic device for three-dimensional dynamic primary human hepatocyte cell culture in the absence of biological or synthetic matrices or coagulants","volume":"10","author":"Goral","year":"2010","journal-title":"Lab Chip"},{"key":"10.1016\/j.ymgme.2026.110241_bb0530","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1002\/bit.21360","article-title":"An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture","volume":"97","author":"Lee","year":"2007","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymgme.2026.110241_bb0535","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2025.154378","article-title":"A scalable human liver-on-a-chip platform for predictive safety assessment","volume":"521","author":"Kulkarni","year":"2026","journal-title":"Toxicology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0540","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aax5516","article-title":"Reproducing human and cross-species drug toxicities using a Liver-Chip","volume":"11","author":"Jang","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymgme.2026.110241_bb0545","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1039\/C8LC00869H","article-title":"In situ differentiation and generation of functional liver organoids from human iPSCs in a 3D perfusable chip system","volume":"18","author":"Wang","year":"2018","journal-title":"Lab Chip"},{"key":"10.1016\/j.ymgme.2026.110241_bb0550","doi-asserted-by":"crossref","DOI":"10.3390\/mi17020180","article-title":"A 3D-printed pump-free multi-organ-on-a-chip platform for modeling the intestine-liver-muscle axis","volume":"17","author":"Kado Abdalkader","year":"2026","journal-title":"Micromachines"},{"key":"10.1016\/j.ymgme.2026.110241_bb0555","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s00204-013-1078-5","article-title":"Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME","volume":"87","author":"Godoy","year":"2013","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0560","doi-asserted-by":"crossref","first-page":"964","DOI":"10.7150\/ijbs.15165","article-title":"Selecting cells for bioartificial liver devices and the importance of a 3D culture environment: a functional comparison between the HepaRG and C3A cell lines","volume":"12","author":"van Wenum","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.ymgme.2026.110241_bb0565","article-title":"The HepG2 cell line as a model for studying metabolic dysfunction-associated Steatotic liver disease","volume":"27","author":"Kotlyarova","year":"2026","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymgme.2026.110241_bb0570","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.biomaterials.2015.08.043","article-title":"A microfluidically perfused three dimensional human liver model","volume":"71","author":"Rennert","year":"2015","journal-title":"Biomaterials"},{"key":"10.1016\/j.ymgme.2026.110241_bb0575","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1080\/03602532.2022.2039688","article-title":"Through a glass, darkly? HepaRG and HepG2 cells as models of human phase I drug metabolism","volume":"54","author":"Stanley","year":"2022","journal-title":"Drug Metab. Rev."},{"key":"10.1016\/j.ymgme.2026.110241_bb0580","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222313135","article-title":"The curious case of the HepG2 cell line: 40 years of expertise","volume":"22","author":"Arzumanian","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymgme.2026.110241_bb0585","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1124\/dmd.109.031831","article-title":"A comparison of whole genome gene expression profiles of HepaRG cells and HepG2 cells to primary human hepatocytes and human liver tissues","volume":"38","author":"Hart","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ymgme.2026.110241_bb0590","doi-asserted-by":"crossref","first-page":"15655","DOI":"10.1073\/pnas.232137699","article-title":"Infection of a human hepatoma cell line by hepatitis B virus","volume":"99","author":"Gripon","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymgme.2026.110241_bb0595","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1007\/s00204-014-1320-9","article-title":"HepaRG microencapsulated spheroids in DMSO-free culture: novel culturing approaches for enhanced xenobiotic and biosynthetic metabolism","volume":"89","author":"Rebelo","year":"2015","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0600","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1002\/jimd.12701","article-title":"Expression and function of the urea cycle in widely-used hepatic cellular models","volume":"6","author":"Makris","year":"2024","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2026.110241_bb0605","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13036-019-0148-5","article-title":"Human three-dimensional in vitro model of hepatic zonation to predict zonal hepatotoxicity","volume":"13","author":"Ahn","year":"2019","journal-title":"J. Biol. Eng."},{"key":"10.1016\/j.ymgme.2026.110241_bb0610","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1124\/dmd.122.000870","article-title":"HepaRG cells adopt zonal-like drug-metabolizing phenotypes under physiologically relevant oxygen tensions and Wnt\/beta-catenin signaling","volume":"50","author":"DiProspero","year":"2022","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ymgme.2026.110241_bb0615","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1093\/toxsci\/kfae018","article-title":"Development of a human liver microphysiological coculture system for higher throughput chemical safety assessment","volume":"199","author":"Ip","year":"2024","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.ymgme.2026.110241_bb0620","doi-asserted-by":"crossref","DOI":"10.1016\/j.dmd.2025.100123","article-title":"Visualization of CYP3A4 expression at both mRNA and protein levels simultaneously at single cell resolution in various conditions using RNAscope combined with immunofluorescence","volume":"53","author":"Jin","year":"2025","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ymgme.2026.110241_bb0625","doi-asserted-by":"crossref","first-page":"5875","DOI":"10.1039\/D5LC00753D","article-title":"Building multiple microenvironmental niches using a customizable 3D printed well insert","volume":"25","author":"Milton","year":"2025","journal-title":"Lab Chip"},{"key":"10.1016\/j.ymgme.2026.110241_bb0630","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ab.2017.07.025","article-title":"Advances in methods for characterization of hepatic urea cycle enzymatic activity in HepaRG cells using UPLC-MS\/MS","volume":"535","author":"Moedas","year":"2017","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.ymgme.2026.110241_bb0635","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-79952-1","article-title":"Differential effects on human cytochromes P450 by CRISPR\/Cas9-induced genetic knockout of cytochrome P450 reductase and cytochrome b5 in HepaRG cells","volume":"11","author":"Heintze","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymgme.2026.110241_bb0640","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.113243","article-title":"Efficient generation of a CYP3A4-T2A-luciferase knock-in HepaRG subclone and its optimized differentiation","volume":"152","author":"Zuo","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ymgme.2026.110241_bb0645","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1124\/dmd.116.069831","article-title":"Contextualizing hepatocyte functionality of cryopreserved HepaRG cell cultures","volume":"44","author":"Jackson","year":"2016","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ymgme.2026.110241_bb0650","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2025.1690384","article-title":"Changes in cultivation parameters impact cytochrome P450 gene transcription in HepaRG cells: implications for in vitro toxicological assessments","volume":"16","author":"Jochum","year":"2025","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0655","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ijpharm.2017.03.080","article-title":"Efficient transfection of xenobiotic responsive element-biosensor plasmid using diether lipid and phosphatidylcholine liposomes in differentiated HepaRG cells","volume":"524","author":"Demazeau","year":"2017","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ymgme.2026.110241_bb0660","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/biot.200900255","article-title":"Highly efficient gene transfer into hepatocyte-like HepaRG cells: new means for drug metabolism and toxicity studies","volume":"5","author":"Laurent","year":"2010","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymgme.2026.110241_bb0665","doi-asserted-by":"crossref","first-page":"12910","DOI":"10.1038\/s41598-019-49402-8","article-title":"A first experience of transduction for differentiated HepaRG cells using lentiviral technology","volume":"9","author":"Pivert","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymgme.2026.110241_bb0670","first-page":"3858","article-title":"Growth of human hepatoma cells lines with differentiated functions in chemically defined medium","volume":"42","author":"Nakabayashi","year":"1982","journal-title":"Cancer Res."},{"key":"10.1016\/j.ymgme.2026.110241_bb0675","first-page":"151","article-title":"Phenotypical stability of a human hepatoma cell line, HuH-7, in long-term culture with chemically defined medium","volume":"75","author":"Nakabayashi","year":"1984","journal-title":"Gan"},{"key":"10.1016\/j.ymgme.2026.110241_bb0680","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.dmpk.2018.03.003","article-title":"Comparison of protein expression between human livers and the hepatic cell lines HepG2, Hep3B, and Huh7 using SWATH and MRM-HR proteomics: focusing on drug-metabolizing enzymes","volume":"33","author":"Shi","year":"2018","journal-title":"Drug Metab. Pharmacokinet."},{"key":"10.1016\/j.ymgme.2026.110241_bb0685","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.ajpath.2010.10.023","article-title":"DNA methylation suppresses expression of the urea cycle enzyme carbamoyl phosphate synthetase 1 (CPS1) in human hepatocellular carcinoma","volume":"178","author":"Liu","year":"2011","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0690","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/282615a0","article-title":"Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line","volume":"282","author":"Aden","year":"1979","journal-title":"Nature"},{"key":"10.1016\/j.ymgme.2026.110241_bb0695","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1126\/science.6248960","article-title":"Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen","volume":"209","author":"Knowles","year":"1980","journal-title":"Science"},{"key":"10.1016\/j.ymgme.2026.110241_bb0700","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.humpath.2009.07.003","article-title":"Hep G2 is a hepatoblastoma-derived cell line","volume":"40","author":"Lopez-Terrada","year":"2009","journal-title":"Hum. Pathol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0705","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.biocel.2006.10.007","article-title":"Ornithine transcarbamylase and arginase I deficiency are responsible for diminished urea cycle function in the human hepatoblastoma cell line HepG2","volume":"39","author":"Mavri-Damelin","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0710","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.1016\/0963-6897(96)00036-X","article-title":"Examination of 7-ethoxycoumarin deethylation and ammonia removal activities in 31 hepatocyte cell lines","volume":"5","author":"Enosawa","year":"1996","journal-title":"Cell Transplant."},{"key":"10.1016\/j.ymgme.2026.110241_bb0715","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"E.P. Consortium","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.ymgme.2026.110241_bb0720","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/s41592-020-0965-y","article-title":"A systematic evaluation of the design and context dependencies of massively parallel reporter assays","volume":"17","author":"Klein","year":"2020","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymgme.2026.110241_bb0725","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41586-024-08430-9","article-title":"Massively parallel characterization of transcriptional regulatory elements","volume":"639","author":"Agarwal","year":"2025","journal-title":"Nature"},{"key":"10.1016\/j.ymgme.2026.110241_bb0730","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0029527","article-title":"Transcriptional regulation of N-acetylglutamate synthase","volume":"7","author":"Heibel","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ymgme.2026.110241_bb0735","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1111\/jcmm.13123","article-title":"The activity of the carbamoyl phosphate synthase 1 promoter in human liver-derived cells is dependent on hepatocyte nuclear factor 3-beta","volume":"21","author":"Chen","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.ymgme.2026.110241_bb0740","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1053\/j.gastro.2009.02.064","article-title":"Y-box binding protein-1 down-regulates expression of carbamoyl phosphate synthetase-I by suppressing CCAAT enhancer-binding protein-alpha function in mice","volume":"137","author":"Chen","year":"2009","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ymgme.2026.110241_bb0745","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.yexcr.2017.12.015","article-title":"Optimizing combination of liver-enriched transcription factors and nuclear receptors simultaneously favors ammonia and drug metabolism in liver cells","volume":"362","author":"Su","year":"2018","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.ymgme.2026.110241_bb0750","doi-asserted-by":"crossref","first-page":"E1294","DOI":"10.1002\/humu.21215","article-title":"Disruption of OTC promoter-enhancer interaction in a patient with symptoms of ornithine carbamoyltransferase deficiency","volume":"31","author":"Luksan","year":"2010","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.ymgme.2026.110241_bb0755","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/S0021-9258(17)42261-7","article-title":"Determination of tissue specificity of the enhancer by combinatorial operation of tissue-enriched transcription factors. Both HNF-4 and C\/EBP beta are required for liver-specific activity of the ornithine transcarbamylase enhancer","volume":"269","author":"Nishiyori","year":"1994","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2026.110241_bb0760","doi-asserted-by":"crossref","first-page":"11125","DOI":"10.1016\/S0021-9258(18)82101-9","article-title":"Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4)","volume":"268","author":"Kimura","year":"1993","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2026.110241_bb0765","doi-asserted-by":"crossref","first-page":"7588","DOI":"10.1016\/S0021-9258(19)57435-X","article-title":"The 5\u2032 flanking region of the ornithine transcarbamylase gene contains DNA sequences regulating tissue-specific expression","volume":"261","author":"Veres","year":"1986","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2026.110241_bb0770","first-page":"1180","article-title":"Promoter and 11-kilobase upstream enhancer elements responsible for hepatoma cell-specific expression of the rat ornithine transcarbamylase gene","volume":"10","author":"Murakami","year":"1990","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.ymgme.2026.110241_bb0775","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.bbrc.2008.09.118","article-title":"Identification of a liver-specific cAMP response element in the human argininosuccinate synthetase gene","volume":"377","author":"Guei","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ymgme.2026.110241_bb0780","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1093\/oxfordjournals.jbchem.a124626","article-title":"Rat argininosuccinate lyase promoter: the dyad-symmetric CCAAT box sequence CCAATTGG in the promoter is recognized by NF-Y","volume":"116","author":"Matsubasa","year":"1994","journal-title":"J. Biochem."},{"key":"10.1016\/j.ymgme.2026.110241_bb0785","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/j.1432-1033.1996.00500.x","article-title":"CCAAT\/enhancer-binding protein beta (C\/EBP beta) binds and activates while hepatocyte nuclear factor-4 (HNF-4) does not bind but represses the liver-type arginase promoter","volume":"236","author":"Chowdhury","year":"1996","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.ymgme.2026.110241_bb0790","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20081888","article-title":"Transcriptional regulation factors of the human mitochondrial aspartate\/glutamate carrier gene, isoform 2 (SLC25A13): USF1 as basal factor and FOXA2 as activator in liver cells","volume":"20","author":"Convertini","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymgme.2026.110241_bb0795","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1002\/humu.24281","article-title":"Noncoding sequence variants define a novel regulatory element in the first intron of the N-acetylglutamate synthase gene","volume":"42","author":"Haberle","year":"2021","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.ymgme.2026.110241_bb0800","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1002\/humu.21553","article-title":"N-carbamylglutamate enhancement of ureagenesis leads to discovery of a novel deleterious mutation in a newly defined enhancer of the NAGS gene and to effective therapy","volume":"32","author":"Heibel","year":"2011","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.ymgme.2026.110241_bb0805","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1002\/humu.23394","article-title":"Disease-causing mutations in the promoter and enhancer of the ornithine transcarbamylase gene","volume":"39","author":"Jang","year":"2018","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.ymgme.2026.110241_bb0810","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-33457-0","article-title":"N-acetylglutamate synthase deficiency due to a recurrent sequence variant in the N-acetylglutamate synthase enhancer region","volume":"8","author":"Williams","year":"2018","journal-title":"Sci. Rep."}],"container-title":["Molecular Genetics and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S109671922600524X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S109671922600524X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:38:38Z","timestamp":1790368718000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S109671922600524X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":162,"journal-issue":{"issue":"1-2","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["S109671922600524X"],"URL":"https:\/\/doi.org\/10.1016\/j.ymgme.2026.110241","relation":{},"ISSN":["1096-7192"],"issn-type":[{"value":"1096-7192","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Human cell-based models for urea cycle research: From gene regulation and ureagenesis to disease modeling and therapeutic development","name":"articletitle","label":"Article Title"},{"value":"Molecular Genetics and Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymgme.2026.110241","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"110241"}}