2018 Fiscal Year Annual Research Report
ヒトiPS肝芽再構成系を用いた血液細胞との相互作用により肝細胞分化制御機構の解明
| Project/Area Number |
18F18101
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| Research Institution | Yokohama City University |
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Principal Investigator |
谷口 英樹 横浜市立大学, 医学研究科, 教授 (70292555)
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| Co-Investigator(Kenkyū-buntansha) |
NIE YUNZHONG 横浜市立大学, 医学部, 外国人特別研究員
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| Project Period (FY) |
2018-04-25 – 2020-03-31
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| Keywords | hiPSC / Organoid / Hepatocyte / Hematopoietic cells / Cell-cell interactions / Liver disease / Liver organogenesis / CD14 |
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| Outline of Annual Research Achievements |
In this study, we are going to understand how the dynamic interactions between hematopoietic and hepatic cells regulate liver development, and to generate the functional liver organoid that can be used for liver disease study and model. For this purpose, we try to establish an organoid to recapitulate hematopoietic-hepatic interactions during early liver organogenesis. In the last year, we successfully established a hematopoietic-hepatic organoid, and found that hematopoietic cells could improve hepatic maturation and hepatic microenvironment helped to maintain the viability of hematopoietic cells. Moreover, we identified that CD14+ cells were that effective hematopoietic population, and noticed that hepatic lineages derived signals could promote the differentiation of CD14+ cells.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
With the established hematopoietic-hepatic organoid, we recapitulated the hematopoietic-hepatic interaction during organoid development, and we figured out the effective hematopoietic population that can promote hepatocyte maturation. These findings confirmed the value of this organoid system in further revealing the dynamic interactions between hematopoietic-hepatic cells in human being. Therefore, this plan is expected to progress smoothly.
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| Strategy for Future Research Activity |
In this year, we are going to further explore the underlying mechanisms of the dynamic interactions by comprehensively analyzing hepatic cells and hematopoietic cells with RNA sequencing and bioinformatics analysis, and try to in vivo verify symbiotic relationship between liver organogenesis and hematopoiesis with animal models. Moreover, we also want to characterize the function of hematopoietic-liver organoid in liver injury mice. Finally, we will summarize the results and publish related papers.
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