2007 Fiscal Year Final Research Report Summary
Profiling of endothelial cell derived stem cell factors associating with the regulation of hematopoietic stem calls
| Project/Area Number |
16390275
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Osaka University (2006-2007)
Kanazawa University (2004-2005) |
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Principal Investigator |
TAKAKURA Nobuyuki Osaka University, Research Institute for Microbial Diseases, Professor (80291954)
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| Co-Investigator(Kenkyū-buntansha) |
UENO Masaya Osaka University, Research Institute for Microbial Diseases, Assistant Professor (20334766)
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| Project Period (FY) |
2004 – 2007
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| Keywords | hematopoietic stem cell / self-renewal / self-renewal / galectin-3 / PSF1 |
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| Research Abstract |
Quiescence is thought to be one of important feature of hematopoietic stem cells (HSCs) for the prevention of exhaustion in bone marrow (BM) adult hematopoiesis. Recently, it has suggested that HSCs change their cell cycle status from cycling population to quiescent one between 3 and 4 weeks after birth. However, the precise molecular mechanism of induction in quiescence of HSCs is not fully understood. Although Tie2, a receptor tyrosine kinase expressed on HSCs has been suggested to regulate quiescence of HSCs, its role is not clearly known. Therefore, we isolated molecules affected by Tie2 activation and analyzed the function of those molecules. We isolated a novel evolutionarily conserved DNA replication factor, PSFI (Partner of SLD5-1) in HSCs. In one-year-old PSF1(+/-) mice, the pool size of stem cells and progenitors is decreased. While young PSF1(+/-) mutant mice develop normally, are fertile, and have no obvious differences in hematopoiesis in the steady state compared with wild-type mice, intravenous injection of 5-fluorouracil (5-FU) is lethal in PSF1(+/-) mice due to a delay in induction of HSC proliferation during ablated BM reconstitution. Our data indicated that PSF1 is required for acute proliferation of HSCs in the BM of mice. Moreover, we found that galactose binding lectin-3 (galectin-3; Gal-3) upregulated by Tie2 activation plays a role in quiescence of HSCs. HSCs from mice harboring conditionally overexpressed Gal-3 under the control of the Tie2 promoter progressed slowly through the cell cycle because of induction of p21. By contrast, cell cycle of Tie2+HSC population from Gal-3-deficient mice was accelerated resulted in exhaustion of HSCs possessing long-term repopulating ability in adult BM. These indicated that Gal-3 is negative regulator of HSC cycling and has a crucial role in inhibition of exhaustion for adult hematopoiesis.
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Research Products
(39 results)
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[Journal Article] Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis2008
Author(s)
Kidoya, H, Ueno, M, Yamada, Y, Mochizuki, N, Nakata, M, Yano, T, Fujii, R, Takakura, N
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] EphB4 overexpression on B16 melanoma cells affects arterial-venous patterning in tumor angiogenesis2007
Author(s)
Huang, X, Yamada, Y, Kidoya, H, Naitoh, H, Nagahama, Y, Kong, L, Katoh, S, Li, W, Ueno, M, Takakura, N
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Journal Title
Cancer Res 67
Pages: 9800-9808
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cardiac stem cells in brown adipose tissue express CD133 and induce bone marrow non-hematopoietic cells to differentiate into cardiomyocytes2007
Author(s)
Yamada, Y, Yokoyama, S, Wang, XD, Fukuda, N, Takakura, N
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Journal Title
Stem, cells 25
Pages: 1326-1333
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel approach for myocardial regeneration with educated cord blood cells cocultured with cells from brown adipose tissue2007
Author(s)
Yamada, Y, Yokoyama, SI, Fukuda, N, Kidoya, H, Huang, XY, Naitoh, H, Satoh, N, Takakura, N
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Journal Title
Biochem Biophys Res Commun 353
Pages: 182-188
Description
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[Journal Article] Inhibition of Axonal Outgrowth in the Tumor Environment : Involvement of Class 3 Semaphorins2007
Author(s)
Vachkov, IH, Huang, X, Yamada, Y, Tonchev, AB, Yamashima, T, Kato, S, Takakura, N
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Journal Title
Cancer Sci 98
Pages: 1192-1197
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification and characterization of mouse PSFI-binding protein, SLD52006
Author(s)
Kong, L, Ueno, M, Itoh, M, Yoshioka, K, Takakura, N
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Journal Title
Biochem Biophys Res Commun 399
Pages: 1204-1207
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Platelet derived growth factor receptor alpha is essential for establishing a microenvironment that supports definitive erythropoiesis2006
Author(s)
Li, WL, Yamada, Y, Ueno, M, Nishikawa, S, Nishikawa, 5, Takakura, N
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Journal Title
J Biochem (Tokyo) 140
Pages: 267-273
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hematopoietic cells regulate the angiogenic switch during tumorigenesis2005
Author(s)
Okamoto, R, Ueno, M, Yamada, Y, Takahashi, N, Sane, H, Takakura, N
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Journal Title
Blood 105
Pages: 2757-2763
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] PSF1 is essential for Early Embryogenesis in mice2005
Author(s)
Ueno, M, Itoh, M, Kong, L, Sugihara, K, Asano, M, Takakura, N
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Journal Title
Mol Cell Biol 25
Pages: 10528-10532
Description
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