Single-cell transcriptomics reveals heterogeneous metabolic profiles in primary human hepatocytes. Single-cell transcriptomics reveals heterogeneous metabolic profiles in primary human hepatocytes

Through scRNA-sequencing of primary human hepatocytes (PHHs), we have identified four subgroups of hepatocytes. A phenotyping 5-probe cocktail (Sanofi-Aventis) has been used to assess their metabolic capacity. Upon cocktail treatment, the characterized four hepatocyte subgroups displayed differential gene expression profiles and exhibited xenobiotic metabolism-related specialization. Intracellular lipid accumulation achieved through loading the cells with free fatty acids (FFA, 2:1 oleic:palmitic acid), differently affected the four subgroups. Moreover, we have shown that intracellular fat accumulation diminishes the drug-related metabolic capacity of hepatocytes.

我们通过对原代人肝细胞（primary human hepatocytes, PHHs）开展单细胞RNA测序（scRNA-sequencing），鉴定出四类肝细胞亚群。本研究采用赛诺菲安万特（Sanofi-Aventis）研发的表型分型5探针组合，对这些亚群的代谢能力进行评估。经该探针组合处理后，上述四类已鉴定的肝细胞亚群呈现出差异基因表达谱，并表现出与异生物质代谢相关的功能特化。通过向细胞中加载游离脂肪酸（free fatty acids, FFA，比例为2:1的油酸与棕榈酸）以诱导细胞内脂质蓄积，该过程对四类肝细胞亚群的影响存在显著差异。此外，我们证实细胞内脂肪蓄积会削弱肝细胞的药物相关代谢能力。