Study on the molecular mechanism of migration of Hematopoietic stem/progenitor cells into hematopoietic microenvironment

造血干/祖细胞迁移至造血微环境的分子机制研究

• 批准号: 14580654
• 负责人: TSUJI Takashi
• 金额: $ 2.3万
• 依托单位: Tokyo University of Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580654/
• 关键词: Hematopoietic stem cells; Hematopoietic microenvironment; Stromal cells; Migration; LIM kinase; Cofilin; 低分子量Gタンパク質; インテグリン

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.

造血干/祖细胞(HS/PC)在造血微环境中的迁移和连续归巢是其增殖和分化的关键。为了研究HS/PC迁移的分子机制，我们使用了一种人红白血病(HEL)细胞系，该细胞系已被鉴定为造血祖细胞系，并在支持造血的基质细胞系下表现出高迁移特性，HEL细胞的迁移是由HEL细胞表面的CD29整合素与Hess-28细胞的黏附介导的，这导致了丝状肌动蛋白的定位，并通过肌动蛋白的细胞骨架重组在膜突起形成了细胞极性。HEL细胞的迁移受到Rho-GTPase家族成员和LIMK1的细胞通透性抑制剂的双重抑制。这些结果表明，由Rho-GTPase/LIMK1/Cofilin途径介导的细胞骨架重组在HESSM28细胞下的迁移中起关键作用。

项目成果

Shu Konakahara et al.: "CD29 INTEGRIN-REORGANI-AND LIMK1/COFILIN-MEDIATED ACTIN REORGANIZATION REGULATES THE MIGRATION OF HEMATOPOJETIC PROGENITOR CELLS UNDERNEATH BONE MARROW STROMAL CELLS"Genes To Cells. 9(4). 345-358 (2004)

Shu Konakahara 等人：“CD29 整合素重组蛋白和 LIMK1/COFILIN 介导的肌动蛋白重组调节骨髓基质细胞下造血祖细胞的迁移”基因到细胞。

Konakahara, S.et al.: "CD29 INTEGRIN- AND LIMK1/COFILIN-MEDIATED ACTIN REORGANIZATION REGULATES THE MIGRATION OF HEMATOPOIETIC PROGENITOR CELLS UNDERNEATH BONE MARROW STROMAL CELLS."Genes to Cells. 9(印刷中). (2004)

Konakahara, S. 等人：“CD29 整合素和 LIMK1/COFILIN 介导的肌动蛋白重组调节造血祖细胞在骨髓基质细胞下的迁移”。基因到细胞 9（出版中）。

Konakahara, S. et al.: "CD29 INTEGRIN- AND LIMK1/COFILIN-MEDIATED ACTIN REORGANIZATION REGULATES THE MIGRATION OF HEMATOPOEETIC PROGENITOR CELLS UNDERNEATH BONE MARROW STROMAL CELLS."Genes to Cells. 9. 345-358 (2004)

Konakahara, S. 等人：“CD29 整合素和 LIMK1/COFILIN 介导的肌动蛋白重组调节造血祖细胞在骨髓基质细胞下的迁移。”基因到细胞。