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. 2024 May 22;630(8015):166–173. doi: 10.1038/s41586-024-07465-2

Extended Data Fig. 9. Intrahepatic cholangiocyte organoids (ICOs) differentiation provides a model to study cellular plasticity.

Extended Data Fig. 9

a) GSEA analysis of cholangiocyte-like-hepatocytes and hepatocyte-like-cholangiocytes from in vivo data (Fig. 3) combined. Top significantly enriched terms are shown. b) qPCR of hepatocyte marker expression in uICOs and dICOs derived from cirrhotic (end stage) livers or healthy donor livers. n = 17 biologically independent experiments for cirrhosis and n = 6 for healthy. Errors bars indicate mean with SD. c) qPCR of KLF6, SOX4 and SERPINE1, which were identified in Fig. 3k as markers of biphenotypic cells, in uICOs and dICOs. n = 10 biologically independent experiments. P-values indicated, two-tailed unpaired t-test. Errors bars indicate SEM). d) qPCR for hepatocyte markers dICOs treated with either DMSO, MK2206 (AKT inhibitor) or rapamycin (mTOR inhibitor) for indicated time. Untreated uICOs included as a control. For CYP3A4 expression n = 6 biologically independent experiments for DMSO, 5 for MK TP1, 4 for MK TP2 and TP3, RAPA TP1 and TP2, 3 for RAPA TP3, 5 for EM control. For ALB expression n = 6 biologically independent experiments for DMSO, 4 for MK TP1 and TP3, 3 for MK TP3, 5 for RAPA TP1, 4 for RAPA TP2, 3 for RAPA TP3, 6 for EM control. P-values are indicated, ordinary one-way ANOVA adjusted for multiple comparisons. Error bars indicate mean with SE. e) Serum insulin levels of patients diagnosed from different MASLD stages. n = 7 biologically independent patients (control), 19 (MASLD), 63 (MASH), 9 (cirrhosis), 3 (end stage). P-values indicated, ordinary one-way ANOVA adjusted for multiple comparisons. Errors bars indicate mean with SD.