بررسی بیان ژن های موثر در سنتز گاما گلوبین قبل و بعد از تمایز سلول های بنیادی خونساز به رده سلول های اریتروئیدی

Background and aim: Induction of fetal hemoglobin (Hb-F) can improve the patients’ symptoms of haemoglobinopathies. Several factors can induce gamma globin gene expression and increased Hb-F levels in patients. In this study, the expression of genes is involved in regulation of gamma globin synthesis such as PIPKII-alpha BCL11a, and miR-30a during CD34+ hematopoietic stem cell differentiation into erythroid lineage was studied. Material and Methods: In this study, CD34+ cells were isolated from umbilical cord blood. Then, CD34+ cells were cultured in differentiation medium. Erythroid colonies were harvested on days 8, 11, 14 and gene expression of gamma globin, PIPKII-alpha, BCL11a, and miR-30a were analyzed by quantitative RT- PCR. Results: The results showed that gene expression of gamma-globin gradually at the 8th day after differentiation started and at 14th day reached to the highest level of its expression. In parallel with increasing the expression of gamma-globin, the expression of PIPKII-alpha increased, while the expression of BCL11a decreased. Moreover, the expression of miR- 30a increased during differentiation into erythroid lineage. Conclusion: The results indicated that increased expression of PIPKII-alpha and decreased expression of BCL11a during CD34+ cells differentiation to erythroid lineage. According to expression pattern of miR-30a and its target genes, PIPKII-alpha and BCL11a, we cannot suppose the inhibitory effect of miR-30a on PIPKII-alpha expression, but due to inhibitory effect of miR-30a on BCL11a gene, we can introduce this microRNA as a regulatory molecule in the induction of Hb-F pathway. However, the further studies are needed to investigate this interaction.