Xia Yang, Yunzhong Nie, Chun Lu, Yang Li, Yoshihito Hayashi, Riana Plummer, Na Luo, Qinglin Li, Toshiharu Kasai, Takashi Okumura, Yumiko Isobe, Kiyoshi Yamaguchi, Yoichi Furukawa, Yan Li, Hideki Taniguchi
Human-induced pluripotent stem cell (hiPSC)-derived liver organoids (LOs) are valuable for studying human liver organogenesis but face challenges in faithfully recapitulating certain processes, like vasculogenesis, due to the lack of specific cell components. Hepatic stellate cells (HSCs), which are liver-specific pericytes and might be crucial for liver vasculogenesis, remain underutilized in developmental studies because of their disease-related status and inefficient generation process. Here, we present an efficient method for generating hiPSC-derived HSCs (hiPSC-HSCs) resembling the transcriptomic profiles of fetal human HSCs. These hiPSC-HSCs exhibit exceptional expandability (>10 5 -fold) while maintaining essential cellular features. Additionally, in entirely hiPSC-derived LOs consisting of HSCs, hepatic endoderm, and endothelial cells, hiPSC-HSCs play a vital role in LO maturation and vascularization, both in vitro and in vivo . This work represents a significant advancement in understanding HSC roles in human liver development, and LOs containing hiPSC-HSCs hold potential in modeling congenital human liver diseases.