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Among the alternative approaches to animal studies, in vitro pooled human hepatocytes have the potential to capture population variability. Here, we examined the effect of the hepatotoxicant thioacetamide on pooled human hepatocytes, divided into five lots, obtained from forty diverse donors. For 24 h, pooled human hepatocytes were exposed to vehicle, 1.33 mM (low dose), and 12 mM (high dose) thioacetamide, followed by RNA-seq analysis. We assessed gene expression variability using heat maps, correlation plots, and statistical variance. We used KEGG pathways and co-expression modules to identify underlying physiological processes\/pathways. The co-expression module analysis showed that the majority of the lots exhibited activation for the bile duct proliferation module. Despite lot-to-lot variability, we identified a set of common differentially expressed genes across the lots with similarities in their response to amino acid, lipid, and carbohydrate metabolism. We also examined efflux transporters and found larger lot-to-lot variability in their expression patterns, indicating a potential for alteration in toxicant bioavailability within the cells, which could in turn affect the gene expression patterns between the lots. Overall, our analysis highlights the challenges in using pooled hepatocytes to understand mechanisms of toxicity.<\/jats:p>","DOI":"10.3390\/ijms25063265","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T13:08:43Z","timestamp":1710335323000},"page":"3265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Probing Liver Injuries Induced by Thioacetamide in Human In Vitro Pooled Hepatocyte Experiments"],"prefix":"10.3390","volume":"25","author":[{"given":"Himanshu","family":"Goel","sequence":"first","affiliation":[{"name":"Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, Frederick, MD 21702, USA"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Printz","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3368-2496","authenticated-orcid":false,"given":"Venkat R.","family":"Pannala","sequence":"additional","affiliation":[{"name":"Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, Frederick, MD 21702, USA"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Diwan M.","family":"AbdulHameed","sequence":"additional","affiliation":[{"name":"Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, Frederick, MD 21702, USA"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Wallqvist","sequence":"additional","affiliation":[{"name":"Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.2174\/1570163813666160114093140","article-title":"From in vitro experiments to in vivo and clinical studies; pros and cons","volume":"12","author":"Saeidnia","year":"2015","journal-title":"Curr. Drug Discov. 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