%0 Journal Article
%A Ayabe, Hiroaki
%A Anada, Takahisa
%A Kamoya, Takuo
%A Sato, Tomoya
%A Kimura, Masaki
%A Yoshizawa, Emi
%A Kikuchi, Shunyuu
%A Ueno, Yasuharu
%A Sekine, Keisuke
%A Camp, J. Gray
%A Treutlein, Barbara
%A Ferguson, Autumn
%A Suzuki, Osamu
%A Takebe, Takanori
%A Taniguchi, Hideki
%+ Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T Optimal hypoxia regulates human iPSC-derived liver bud differentiation through intercellular TGFB signaling  : 
%G eng
%U https://hdl.handle.net/21.11116/0000-0001-BFEE-D
%R 10.1016/j.stemcr.2018.06.015
%7 2018-07-19
%D 2018
%8 14.08.2018
%* Review method: peer-reviewed
%X Timely controlled oxygen (O2) delivery is crucial for the developing liver. However, the influence of O2 on intercellular communication during hepatogenesis is unclear. Using a human induced pluripotent stem cell-derived liver bud (hiPSC-LB) model, we found hypoxia induced with an O2-permeable plate promoted hepatic differentiation accompanied by TGFB1 and TGFB3 suppression. Conversely, extensive hypoxia generated with an O2-non-permeable plate elevated TGFBs and cholangiocyte marker expression. Single-cell RNA sequencing revealed that TGFB1 and TGFB3 are primarily expressed in the human liver mesenchyme and endothelium similar to in the hiPSC-LBs. Stromal cell-specific RNA interferences indicated the importance of TGFB signaling for hepatocytic differentiation in hiPSC-LB. Consistently, during mouse liver development, the Hif1a-mediated developmental hypoxic response is positively correlated with TGFB1 expression. These data provide insights into the mechanism that hypoxia-stimulated signals in mesenchyme and endothelium, likely through TGFB1, promote hepatoblast differentiation prior to fetal circulation establishment.
%K liver bud; organogenesis; organoid; oxygen; iPSC; differentiation; hypoxia
%J Stem Cell Reports
%V 11
%N 2
%& 306
%P 306 - 316
%I Cell Press; Elsevier 
%C Cambridge; New York 
%@ 2213-6711