Related Experiment Video
Updated: Feb 7, 2026

Efficient Differentiation of Human Pluripotent Stem Cells into Liver Cells
Published on: June 11, 2019
Optimal Hypoxia Regulates Human iPSC-Derived Liver Bud Differentiation through Intercellular TGFB Signaling
Hiroaki Ayabe1, Takahisa Anada2, Takuo Kamoya2
1Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan.
Abstract:
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.
More Related Videos
Related Concept Videos
What is Cell Signaling?
Hypoxia
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
Master Transcription Regulators
The Tongue and Taste Buds
Taste Buds and Receptors
GTPases and their Regulation
Large G-proteins,...

