2017 Fiscal Year Final Research Report
Analysis on molecular mechanisms regulating fetal liver stem cells, hepatoblasts, by using a novel organoid culture system
| Project/Area Number |
16K21106
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
Cell biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 肝芽細胞 / 肝芽腫 / 幹細胞 / Hippoシグナル / Wntシグナル / オルガノイド培養法 |
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| Outline of Final Research Achievements |
In this study, we aimed to reveal mechanisms regulating fetal liver stem cells, hepatoblasts, and also to understand how disturbance of such mechanisms leads to the childhood liver cancer, hepatoblastoma. By using a newly developed in vitro culture method of hepatoblasts, we found that activation of the Hippo pathway effector, YAP, confers long-term self-renewal ability on hepatoblasts, while activation of beta-catenin promotes Wnt signaling-independent growth of hepatoblasts. Activation of both YAP and beta-catenin induced expression of IGF-1, thereby promoting growth factor-independent survival and proliferation of hepatoblasts. Moreover, transplantation of cultured and genetically modified hepatoblasts showed that simultaneous activation of YAP, beta-catenin, and c-Myc induces formation of hepatoblastoma-like tumors in immunodeficient mice. These results identify novel mechanisms regulating hepatoblast cell fate and suggest that disturbance of the mechanisms leads to hepatoblastoma.
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| Free Research Field |
細胞生物学
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