Extended Data Fig. 8: Drug metabolism in HHOs.
From: Generation of human adult hepatocyte organoids with metabolic functions
a. The expression of genes related to cytochrome P450-mediated drug metabolism in PHHs, eHHOs, and dHHOs based on RNA-seq data. b. A workflow for analyzing basal and drug-induced CYP activity (top). The percentage of 2D plating efficiency of PHH and their derivative dHHOs (bottom). Total culture days are shown in parentheses. c. Basal CYP activities in PHHs and dHHOs related to Fig. 3j. Workflow in b. Drugs used for CYP induction indicated in parenthesis. Three donors at different time points. Each dot shows an experimental replicate. dHHOs were cultured for the indicated durations before 2D plating. Error bars show mean ± SD for PY12 (PHH; n = 5, dHHO; n = 5 with 4 conditions), PY30 (PHH; n = 8, dHHO; n = 5 with 4 conditions, and PY39b (PHH; n = 7 with 2 replicates, dHHO condition; n = 3 with 2 conditions). d. Drug-induced activity of CYPs in PHHs and dHHOs. Data from HHOs derived from three different donors. Each dot shows one well. Data are shown as mean ± SD of triplicates. e. Coumarin metabolism by CYP2A6, UGT, and SULT. f. Measurement of coumarin metabolites in PHHs and dHHOs with LC-MS/MS. The proportion of unconjugated and conjugated derivatives is shown. g. Dose-response curves of acetaminophen treatment on dHHOs. Organoid viability and damage was measured using ATP activity (top) and lactate dehydrogenase (LDH) release (bottom), respectively. Error bars show mean ± SD of three technical replicates for each condition.
