miR-451 Up-regulation, Induce Erythroid Differentiation of CD133+cells Independent of Cytokine Cocktails

Abstract

Objective(s): Erythropoiesis is regulated by some extrinsic and intrinsic factors as microRNAs (miRNAs). miRNAs are endogenously small non-coding regulatory RNAs which play vital roles in the variety of cellular fate, critical processes; growth, apoptosis, metabolism, survival of the cells and specially differentiation. Several miRNAs such as miR-16 and miR-451 have been shown to be correlated with erythroid differentiation. Taking into account the importance of miRNAs in cellular differentiation, the goal of the present study was to examine the role of miRNAs in hematopoietic stem cells (HSC) differentiation into the erythroid cells in the absence of growth factors and stimulatory cytokines. Materials and Methods: CD133+ stem cells were infected with lentiviruses containing miR-451/miR-16 precursor sequence, erythroid differentiation was evaluated using RT-PCR for hemoglobin chains and surface antigens, also by banzidine staining. Results: MiR-451up-regulation, but not miR-16, could induce α, β and γ-globin expression in CD133+ cells and have strong correlation with appearance of CD71 and CD235a markers in these cells. Moreover, miR-451 up-regulation increases the banzidine positive cells to ~ %40. Conclusion: Our results provide strong evidence that miR-451 up-regulation strongly induces erythroid differentiation and maturation of CD133+ stem cells. Hence, this method may provide a useful technique for the production of artificial blood RBC and be used as a new strategy for gene therapy of hemoglobinopathies, such as β-thalassemias and sickle cell anemia.

Keywords

• Erythropoiesis CD133+ microRNA miR-451 miR-16