2013 Fiscal Year Final Research Report
Characterization and exploration of bone marrow niche regulators for hematopoietic stem cells
| Project/Area Number |
23390256
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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 | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
HARA Takahiko 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, プロジェクトリーダー(参事研究員) (80280949)
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| Co-Investigator(Kenkyū-buntansha) |
KITAJIMA Kenji 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (10346132)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | 造血幹細胞 / 骨髄ニッチ |
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| Research Abstract |
To understand how hematopoietic stem cells (HSCs) interact with bone marrow niche, we investigated functions of chemokine CXCL14 and cilia protein CMG-1, and searched for downstream effector molecules of the HSC-acting transcription factor Lhx2. We discovered that CXCL14 binds to CXCR4 with high affinity and completely inhibits the CXCL12-mediated migration of hematopoietic progenitor cells. However, number and frequency of bone marrow HSCs in CXCL14 knockout mice were similar as those in wild type mice. Same thing was true in bone marrows of HSC-specific CMG-1 conditional knockout mice. Lastly, we searched for membrane proteins that are relevant to the undifferentiated status of HSCs by using an Lhx2-trigerred HSC expansion culture of ES cells. As a result, we identified several candidate genes such as Biglycan, Esam1, and Jam3.
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