Transcriptomic Cross‐Species Analysis of Chronic Liver Disease Reveals Consistent Regulation Between Humans and Mice

• DOI: 10.1002/hep4.1797
• Publication Date: 2021-08-28T07:39:35Z
• Authors: Christian H. Holland; Ricardo O. Ramire...; Maiju Myllys; Reham Hassan; Karolina Edlund; Ute Hofmann; Rosemarie Marchan; Cristina Cadenas; Jörg Reinders; Stefan Hoehme; Abdel‐latif Seddek; Steven Dooley; Verena Keitel; Patricio Godoy; Brigitte Begher‐T...; Christian Trautwein; Christian Rupp; Sebastian Mueller; Thomas Longerich; Jan G. Hengstler; Julio Saez‐Rodriguez; Ahmed Ghallab
• Keywords: Immunostaining

Mouse models are frequently used to study chronic liver diseases (CLDs). To assess their translational relevance, we quantified the similarity of commonly mouse human CLDs based on transcriptome data. Gene‐expression data from 372 patients were compared with acute and consisting 227 mice, additionally nine published gene sets models. Genes consistently altered in humans mice mapped cell types single‐cell RNA‐sequencing validated by immunostaining. Considering top differentially expressed genes, between varied among depended period damage induction. The highest recall (0.4) precision (0.33) observed for model 12‐months induction CCl 4 a Western diet, respectively. up‐regulated enriched inflammatory developmental processes, mostly cholangiocytes, macrophages, endothelial mesenchymal cells. Down‐regulated genes metabolic processes hepatocytes. Immunostaining confirmed regulation selected type specificity. that both showed higher respect than exclusively or genes. Conclusion: Similarly regulated identified. Despite major interspecies differences, detected 40% significantly CLD. relevance individual can be assessed at https://saezlab.shinyapps.io/liverdiseaseatlas/.