Roles of BMP signaling in maintenance of cell stemness
| Project/Area Number |
24390070
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MIYAZONO Kohei 東京大学, 医学(系)研究科(研究院), 教授 (90209908)
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| Co-Investigator(Renkei-kenkyūsha) |
KOINUMA Daizo 東京大学, 大学院医学系研究科, 准教授 (80375071)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | 細胞医化学 / ゲノム医化学 / 細胞内シグナル伝達 / 発生医学 |
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| Outline of Final Research Achievements |
BMPs are key serum-derived factors that act to sustain self-renewal and pluripotency of mouse ES cells. In contrast, human ES cells share defining features with mouse epiblast stem cells (mEpiSC). BMP-4 induces differentiation of mEpiSCs into extraembryonic lineage or mesendoderm. We found that the BMP-Smad pathway is dispensable for maintaining naive pluripotency, and that the transcriptional factor KLF4 plays a key role in the suppression of Smad1 activity. We also found that the MEK5-ERK5 pathway mediates BMP-4-induced self-renewal of mESCs by inducing KLF2.
We have investigated the roles of BMPs in regulation of glioma-initiating cells (GICs). In the orthotopic transplantation model, BMP signaling repressed the tumorigenic activity through loss of stemness properties of GICs. We further performed DNA microarray and RNA-seq analyses to identify novel target genes of BMP signaling in GICs, and found that PRRX1 plays an important role in regulation of the differentiation of GICs.
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Report
(5 results)
Research Products
(18 results)
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[Journal Article] BMP Sustains Embryonic Stem Cell Self-Renewal through Distinct Functions of Different Kruppel-like Factors.2016
Author(s)
Morikawa M, Koinuma D, Mizutani A, Kawasaki N, Holmborn K, Sundqvist A, Tsutsumi S, Watabe T, Aburatani H, Heldin CH, Miyazono K.
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Journal Title
Stem Cell Reports.
Volume: 6
Issue: 1
Pages: 64-73
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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