| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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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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