2003 Fiscal Year Final Research Report Summary
Study on the molecular mechanism of migration of Hematopoietic stem/progenitor cells into hematopoietic microenvironment
| Project/Area Number |
14580654
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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 |
Functional biochemistry
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
TSUJI Takashi Tokyo University of Science, Faculty of Industrial Science and Technology, Associate Professor, 基礎工学部, 助教授 (50339131)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Kensaku Graduate School of Life Sciences, Tohoku University, Department of Biomolecular Sciences, Professor, 大学院・生命科学研究科, 教授 (70128396)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Hematopoietic stem cells / Hematopoietic microenvironment / Stromal cells / Migration / LIM kinase / Cofilin |
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| Research Abstract |
Migration and successive homing of hernatopoietic stem/progenitor cells(HS/PCs)into hematopoietic microenvironments are critical to their proliferation and differentiation.To investigate molecular mechanisms underlying HS/PC migration, we used a human erythroleukaemia(HEL) cell line which has been characterized as a hematopoietic progenitor cell line and displays high migratory properties underneath the hematopoietic-supportive stromal cell line, HESS-M28.HEL cell migration is mediated by the adhesion of the CD29 integrin on HEL cells to HESS-28 cells which leads to the localization of filamentous actin and formation of cell polarity at membrane protrusions via actin cytoskeleton reorganization.HEL cell migration is inhibited by both dominant negative forms of the Rho-GTPase family members and a cell permeable inhibitor of LIMK1, S3 peptide.Expression of constitutively active-or inactive-forms of cofilin also inhibits HEL cell migration and phosphorylated cofilin is localized to the front protrusions of HEL cells.These results suggest that cytoskeleton reorganization mediated by a Rho-GTPase/LIMK1/cofilin pathway plays a critical role in the migration of HEL cells underneath HESSM28 cells.
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