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

造血干细胞/祖细胞（HS/PCs）在造血微环境中的迁移和连续归巢对其增殖和分化至关重要。为了研究HS/PC迁移的分子机制，我们使用了人类红白血病（HEL）细胞系，该细胞系具有造血祖细胞系的特征，并在造血支持基质细胞系HESS-M28下显示出高迁移特性。HEL细胞迁移是由HEL细胞上的CD29整合素粘附到HESS-28细胞介导的，从而导致丝状肌动蛋白的定位，并通过肌动蛋白细胞骨架重组在膜突起处形成细胞极性。HEL细胞的迁移受到Rho-GTPase家族成员的显性阴性形式和LIMK1， S3肽的细胞渗透性抑制剂的抑制。组成活性或非活性形式的cofilin的表达也抑制HEL细胞的迁移，磷酸化的cofilin定位于HEL细胞的前突起。这些结果表明，Rho-GTPase/LIMK1/cofilin通路介导的细胞骨架重组在HEL细胞在HESSM28细胞下的迁移中起关键作用。

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.