2006 Fiscal Year Final Research Report Summary
Analysis of switching mechanism between self-renewal and differentiation in ES cells
| Project/Area Number |
17570174
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Developmental biology
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| Research Institution | Kanazawa University |
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Principal Investigator |
KOIDE Hiroshi Graduate School of Medical Science, Associate Professor, 医学系研究科, 助教授 (70260536)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOTA Takashi Graduate School of Medical Science, Professor, 医学系研究科, 教授 (50134622)
SHIBATA Shinwa Graduate School of Medical Science, Assistant Professor, 医学系研究科, 助手 (40372487)
MIURA Miwako Graduate School of Medical Science, Researcher, 医学系研究科, 研究支援者 (00377417)
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| Project Period (FY) |
2005 – 2006
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| Keywords | stem cells / self-renewal / cell differentiation / embryonic stem cells / signal transduction |
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| Research Abstract |
In this study, we tried to clarify the molecular mechanism of switching from undifferentiated ES cells to differentiated ES cells, which is regulated by leukemia inhibitory factor (LIF) in mouse ES cells.
At first, using DNA microarray method, we searched for molecules whose expression is restricted to either self-renewing ES cells or differentiating ES cells, and found several interesting genes, such as transcription factors (Zfp 57 and GABPα), a polycomb family protein (Eed), an oncoprotein (β-catenin) and a novel gene (STAT3-activated gene 3, S3A3).
We next examined the role of these molecules in ES cells. Zfp57, though it is a good marker for self-renewing ES cells, was turned out to be dispensable for ES cell self-renewal. Eed was required for the maintenance of the "complete" undifferentiated state. Although S3A3 is dispensable for ES cell self-renewal, knockout of this gene promoted differentiation of ES cells into endoderm, suggesting that S3A3 is a negative regulator of endoderm differentiation. We thus renamed this gene as STAT3 downstream gene and differentiation regulator (Sddr). We also found that GABPα controls Oct-3/4 expression through suppression of Oct-3/4 repressors, and that LIF stimulates the stabilization of nuclear β-catenin, which in turn binds with Oct-3/4 to induce the expression of Nanog. These results suggest that LIF regulates the switching from self-renewing ES cells to differentiated ES cells through control of a variety of molecules, including Eed, Sddr, GABPα and β-catenin.
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[Journal Article] GABPa regulates Oct-3/4 expression in mouse embryonic stem cells.2007
Author(s)
Kinoshita, K., Ura, H., Akagi, T., Usuda, M., Koide, H., Yokota, T.
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Journal Title
Biochem. Biophys. Res. Commun. 353
Pages: 686-691
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identificatioi of Zfp-57 as a downstream molecule of STAT3 and Oct-3/4 in embryonic stem cells.2005
Author(s)
Akagi, T., Usuda, M., Matsuda, T., Ko, M.S.H., Niwa, H., Asano, M., Koide, H., Yokota, T.
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Journal Title
Biochem. Biophys. Res. Commun. 331
Pages: 23-30
Description
「研究成果報告書概要(欧文)」より
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