Generation of expandable hepatocyte organoids with multipolar organization from human embryonic stem cells

Within this differentiation platform, spherical hepatocyte organoids (S-heporg) spontaneously emerged alongside G-heporgs. Similar to primary heporgs, differentiated G-heporgs exhibited high ALB expression and expansion capability, whereas the S-heporgs lacked both characteristics.

Comparative analysis revealed that IGF2 stimulates G-heporg formation. Moreover, we found that targeted modulation of the Hippo-YAP pathway overcame long-term expansion limitations in G-heporgs. Crucially, the differentiated and expandable G-heporgs developed multipolar architectures with functional BC networks, recapitulating the polarity characteristic of primary hepatocytes.