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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| Project Status |
Completed (Fiscal Year 2015)
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| 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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| Keywords | 組織幹細胞 / 肝臓 / 肝細胞 / 胆管上皮細胞 / 肝幹細胞 / 肝幹前駆細胞 / 分化可塑性 / 転写因子 |
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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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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Soluble lutheran/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patients and modulates cellular interaction with laminin-511 in vitro2014
Author(s)
Kikkawa Y, Miwa T, Tanimizu N, Kadoya Y, Ogawa T, Katagiri F, Hozumi K, Nomizu M, Mizuguchi T, Hirata K, Mitaka T
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Journal Title
Experimental Cell Research
Volume: 328
Issue: 1
Pages: 197-206
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Wnt5a Signaling Mediates Biliary Differentiation of Fetal Hepatic Stem/Progenitor Cells2013
Author(s)
Kakinuma S, Kiyohashi K, Kamiya A, Sakamoto N, Nitta S, Yamanaka H, YoshinoK, Fujiki J, Murakawa M, Kusano-Kitazume A, Shimizu H, Okamoto R, Azuma S, Nakagawa M, Asahina Y, Tanimizu N, Kikuchi A, Nakauchi H, and *WatanabeM
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Journal Title
Hepatology
Volume: (in press)
Issue: 6
Pages: 2502-2513
DOI
Related Report
Peer Reviewed
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