Uncovering the mechanisms underlying maintenance of undifferentiated states in somatic cells and its application for cancer research
| Project/Area Number |
19689011
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Gifu University |
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Principal Investigator |
YAMADA Yasuhiro Gifu University, 大学院・医学系研究科, 准教授 (70313872)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2009: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2008: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2007: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | Rest / ES細胞 / Pluripotency / 大腸発がん / Nrsf / 分化 / 未分化性維持 / NRSF / Stem cell / Carcinogenesis / Progenitor cell / beta-catenin |
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| Research Abstract |
The pluripotency of ES cells is maintained by the coordinated expression of genes in the core regulatory circuitry that includes Oct3/4, Sox2 and Nanog. Rest (also called Nrsf) is abundantly expressed in ES cells and it is a target of the Oct3/4-Sox2-Nanog regulatory network core circuitry. However, the functional significance of Rest in the maintenance of pluripotency in ES cells remains controversial. We herein generated Rest conditional knock-out and REST-inducible ES cell lines. The conditional ablation of Rest showed that Rest is not indispensible for the maintenance of pluripotency, however, it is involved in the suppression of self-renewal genes upon the early differentiation of ES cells. Consistently, the forced expression of REST results in the rapid differentiation of ES cells. Our results indicate that Rest is not necessary for the maintenance of ES cells, while further suggest that the Rest transcriptional repressor is an external factor connecting to the Oct3/4-Sox2-Nanog core regulatory circuitry to induce the early differentiation of ES cells.
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Report
(4 results)
Research Products
(52 results)
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[Journal Article] Further upregulation of β-catenin/Tcf transcription is involved in the development of macroscopic tumors in the colon of Apc Min/+ mice.2008
Author(s)
Oyama T, Yamada Y, Hata K, Tomita H, Hirata A, Sheng HQ, Hara A, Aoki H, Kunisada T, Yamashita S, Mori H
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Journal Title
Carcinogenesis 29
Pages: 666-672
Related Report
Peer Reviewed
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[Journal Article] Preventive effect of fermented brown rice and rice bran on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats.2008
Author(s)
Tomita H, Kuno T, Yamada Y, Oyama T, Asano N, Miyazaki Y, Baba S, Taguchi A, Hara A, Iwasaki T, Kobayashi H, Mori H
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Journal Title
Oncol Rep 19
Pages: 11-15
Related Report
Peer Reviewed
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[Journal Article] Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing.2007
Author(s)
Linhart HG, Lin H, Yamada Y, Moran E, Steine EJ, Gokhale S, Lo G, Cantu E, Ehrich M, He T, Meissner A, Jaenisch R
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Journal Title
Genes Dev 21
Pages: 3110-3122
Related Report
Peer Reviewed
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[Journal Article] Development of gastric tumors in Apc Min/+ mice by the activation of the β-catenin/Tcf signaling pathway.2007
Author(s)
Tomita H, Yamada Y, Oyama T, Hata K, Hirose Y, Hara A, Kunisada T, Sugiyama Y, Adachi Y, Linhart H, Mori H
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Journal Title
Cancer Res 67
Pages: 4079-87
Related Report
Peer Reviewed
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