biostudies-literatureKuse YMinistry of Education, Culture, Sports, Science and Technology (MEXT)Japan Agency for Medical Research and Development (AMED)2493https://www.ebi.ac.uk/biostudies/studies/S-EPMC11906828biostudies-literatureUnknown16(1)Organoids derived from human induced pluripotent stem cells (hiPSC) are potentially applicable for regenerative medicine. However, the applications have been hampered by limited organoid size and function as a consequence of a lack of progenitor expansion. Here, we report the recapitulation of progenitor expansion in hiPSC-liver organoids based on the analysis of mouse development. Visualization of blood perfusion and oxygen levels in mouse embryos reveals a transient hypoxic environment during hepatoblast expansion, despite active blood flow. During this specific stage, the placenta expresses various growth factors. Human and mouse placenta-liver interaction analysis identifies various placenta-derived factors. Among them, IL1α efficiently induces the growth in hiPSC-liver organoids as weNature communicationsPlacenta-derived factors contribute to human iPSC-liver organoid growth.PMC1190682819K18034JP13bm030400222K16440JP22bm0304002h031021H04830JP23bm1223007Matsumoto SKasai TTsuzuki SUeno YOba TKuse YFurukawa YTadokoro TCarolina EYamabe STaniguchi HTanimizu NYamaguchi KOkumura TfalsePlacenta-derived factors contribute to human iPSC-liver organoid growth.Organoids derived from human induced pluripotent stem cells (hiPSC) are potentially applicable for regenerative medicine. However, the applications have been hampered by limited organoid size and function as a consequence of a lack of progenitor expansion. Here, we report the recapitulation of progenitor expansion in hiPSC-liver organoids based on the analysis of mouse development. Visualization of blood perfusion and oxygen levels in mouse embryos reveals a transient hypoxic environment during hepatoblast expansion, despite active blood flow. During this specific stage, the placenta expresses various growth factors. Human and mouse placenta-liver interaction analysis identifies various placenta-derived factors. Among them, IL1α efficiently induces the growth in hiPSC-liver organoids as we2025-01-01T00:00:00Z2025 Mar2026-04-08T19:48:37.734Z2025-04-05T22:08:05.308ZS-EPMC119068284008240210.1038/s41467-025-57551-w