MEK1 activation enhances the ex vivo proliferation of haematopoietic stem/progenitor cell.

Haematopoietic stem/progenitor cell (HSPC) integrates intracellular signal network from growth factors (GFs) and utilizes its proliferation feature to generate high yields of transplantable cells upon ex vivo culture. However, the molecular basis for HSPC activation and proliferation is not completely understood. The goal of this study was to investigate proliferation regulator in the downstream of GFs and develop HSPC expansion strategy. Microarray and Ingenuity Pathway Analysis were performed to evaluate differentially expressed genes in cytokine-induced CD34 cells after ex vivo culture. We identified that MEK1 was a potential HSPC proliferation regulator, which represented indispensable roles and MEK1 silence attenuated the proliferation of HSPC. Notably, 500 nM MEK1 agonist, PAF C-16, increased the numbers of phenotypic HSPC and induced cell cycling of HSPC. The PAF C-16 expanded HSPC demonstrated comparative clonal formation ability and secondary expansion capacity compared to the vehicle control. Our results provide insights into regulating the balance between proliferation and commitment of HSPC by targeting the HSPC proliferation-controlling network. This study demonstrates that MEK1 critically regulates HSPC proliferation and cell production in the ex vivo condition for transplantation.