2015 Fiscal Year Final Research Report
Role of liver stem/progenitor cells in development and regeneration
| Project/Area Number |
25460271
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 組織幹細胞 / 肝臓 / 肝細胞 / 胆管上皮細胞 |
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| Outline of Final Research Achievements |
We isolated liver stem/progenitor cells (LPCs) as EpCAM(+) cells from developing livers. Neonatal EpCAM(+) cells clonally proliferated and differentiated to functional hepatocytes in the presence of OSM and Matrigel in vitro. When they were transplanted to nude mice treated with retrorsine and 70% partial hepatectomy, neonatal EpCAM(+) cells are engrafted as hepatocytes and cholangiocytes in recipient liver tissue. In contrast, adult EpCAM(+) cells barely differentiate to hepatocytes. A transcription factor grainyhead-like 2 (Grhl2), which is strongly expressed in adult EpCAM(+) cells, suppressed hepatocytic differentiation of neonatal EpCAM(+) cells. Moreover, by comparing hepatocyte progenitor cell lines with or without Grhl2, miR122 was identified as a microRNA downregulated by Grhl2. We conclude that Grhl2 suppresses hepatocytic differentiation of EpCAM(+) cells by downregulating miR122.
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| Free Research Field |
細胞生物学
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