miR-17 promotes expansion and adhesion of human cord blood CD34 + cells in vitro

Introduction We have recently found that miR-17 is necessary in the cell-extrinsic control of cord blood (CB) CD34 + cell function. Here, we demonstrated that the proper level of miR-17 is also necessary in the cell-intrinsic control of the hematopoietic properties of CB CD34 + cells. Methods The miR-17 overexpression and knockdown models were created using primary CB CD34 + cells transfected by the indicated vectors. Long-term culture, colony forming, adhesion and trans-well migration assays were carried out to investigate the function of miR-17 on CB CD34 + cells in vitro. NOD prkdc scid Il2rg null mice were used in a SCID repopulating cell assay to investigate the function of miR-17 on CB CD34 + cells in vivo. A two-tailed Student’s t -test was used for statistical comparisons. Results In vitro assays revealed that ectopic expression of miR-17 promoted long-term expansion, especially in the colony-forming of CB CD34 + cells and CD34 + CD38 − cells. Conversely, downregulation of miR-17 inhibited the expansion of CB CD34 + cells. However, the overexpression of miR-17 in vivo reduced the hematopoietic reconstitution potential of CB CD34 + cells compared to that of control cells. The increased expression of major adhesion molecules in miR-17 overexpressed CB CD34 + cells suggests that the adhesion between miR-17 overexpressed CB CD34 + cells and their niche in vivo is regulated abnormally, which may further lead to the reduced hematopoietic reconstitution capability of 17/OE cells in engrafted mice. Conclusion We conclude that the proper expression of miR-17 is required, at least partly, for normal hematopoietic stem cell–niche interaction and for the regulation of adult hematopoiesis.