As increase cell proliferation of hematopoietic stem cells (HS) cells has a significant impact on clinical application, to investigate the molecular mechanism underlying the regulation of HS cell expansion is thus important. This study aims to investigate the molecular signaling involves in regulating cell proliferation of mouse HS cells derived from pluripotent embryonic stem (ES) cells. We have first established the protocol to differentiate mouse ES cells into HS cells and performed the gene expression profile by microarray analysis. Among the genes expression altered during the hematopoietic differentiation, we found a significantly reduction of 14-3-3{sigma} in mouse ES derived HS cells. Re-introduced 14-3-3{sigma} overexpression significantly increased HS cell growth and number of hematopoietic forming colonies. In addition, suppression of GSK-3β with inhibitor enhanced, but PI-3K inhibitor reduced HS cell proliferation. Taken together, 14-3-3{sigma} combined with PI-3K/Akt and GSK-3β/β-catenin signals are considered as critical targets for inducing HS cell expansion.
