Transcriptomic Analysis of Hepatic Cells in Multicellular Organotypic Liver Models

In this study, genome-wide gene expression profiles of primary hepatocytes and liver sinusoidal endothelial cells (LSECs) were measured at day 12 for each cell culture system using Affymetrix GeneChips and analyzed via Gene Set Enrichment Analysis (GSEA). The culture systems analyzed include the commonly used collagen sandwich and monolayers of hepatocytes, as well as 3-dimensional (3D) engineered liver models that contain hepatocytes and LSECs (3DHL) and hepatocytes, LSECs, and Kupffer cells (3DHLK). Our results highlight the up-regulation of several hepatocyte specific functions in hepatocytes and a novel interplay between Ppara signaling and bile acid biosynthesis in LSECs.本研究采用Affymetrix基因芯片（Affymetrix GeneChips），于细胞培养第12天对各培养体系中的原代肝细胞（primary hepatocytes）与肝窦内皮细胞（liver sinusoidal endothelial cells, LSECs）进行全基因组基因表达谱检测，并通过基因集富集分析（Gene Set Enrichment Analysis, GSEA）完成数据分析。本研究涉及的细胞培养体系涵盖两类经典肝细胞培养体系：常用的胶原三明治培养体系与肝细胞单层培养体系，同时包含两种三维工程化肝脏模型：其一共培养原代肝细胞与肝窦内皮细胞（3DHL），其二共培养原代肝细胞、肝窦内皮细胞与库普弗细胞（Kupffer cells, 3DHLK）。本研究结果表明，肝细胞内多项肝细胞特异性功能相关基因呈现上调表达，且在肝窦内皮细胞中发现Ppara信号通路与胆汁酸生物合成之间存在全新的交互调控关联。