Characterization of Pro-Fibrotic Signaling Pathways in Human Hepatic Organoids

Due to the limitations of available in vitro systems and animal models, we lack a detailed understanding of the pathogenetic mechanisms and have minimal treatment options for liver fibrosis. To overcome this barrier, we engineered a live cell imaging system that identifies collagen producing cells in a human multi-lineage hepatic organoid. This system was adapted for use as a microwell-based platform (i.e., microHOs) where exposure to PDGF or TGFb1 induced the formation of thick collagen fibers. Transcriptomic analysis revealed that TGFb1 converted mesenchymal cells into collagen producing myofibroblasts. To characterize the pro-fibrotic effects of PDGFB and TGFB1 at transcriptome level, scRNA-Seq data was generated from day 9 control hepatoblast cultures and from day 21 control, TGFB1-treated or PDGFB-treated microHOs.