Igarashi, Ryo

写真a

Affiliation

School of Medicine, Department of Biochemistry (Shinanomachi)

Position

Project Assistant Professor (Non-tenured)/Project Research Associate (Non-tenured)/Project Instructor (Non-tenured)
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  • Generation of human adult hepatocyte organoids with metabolic functions

    Igarashi R., Oda M., Okada R., Yano T., Takahashi S., Pastuhov S., Matano M., Masuda N., Togasaki K., Ohta Y., Sato S., Hishiki T., Suematsu M., Itoh M., Fujii M., Sato T.

    Nature 641 ( 8065 ) 1248 - 1257 2025.05

    ISSN  00280836

    　View Summary

    Proliferating hepatocytes often undergo ductal metaplasia to balance the energy trade-off between cellular functions and replication, hindering the expansion of human adult hepatocytes with functional competency<sup>1</sup>. Here we demonstrate that the combined activation of Wnt and STAT3 signalling enables long-term self-renewal of human adult hepatocyte organoids. YAP activation facilitates hepatocyte proliferation but commits it towards the biliary duct lineage. By contrast, STAT3 activation by oncostatin M induces hepatocyte proliferation while counteracting ductal metaplasia and maintaining the hepatic identity. Xenotransplanted hepatocyte organoids repopulate the recipient mouse liver and reconstitute the metabolic zonation structure. Upon niche factor removal and hormone supplementation, hepatocyte organoids form cord-like structures with bile canalicular networks and exhibit major liver metabolic functions comparable to those of in vivo hepatocytes. Hepatocyte organoids are amenable to gene editing, prompting functional modelling of inherent metabolic liver diseases. The new culture system offers a promising avenue for developing therapeutic strategies against human liver diseases.

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