Mir-218 contributes to the transformation of 5-Aza/GF induced umbilical cord mesenchymal stem cells into hematopoietic cells through the MITF pathway

Kaimeng Hu, Chen Xu, Haitao Ni, Zhenyu Xu, Yue Wang, Sha Xu, Kaihong Ji, Jun Xiong, Houqi Liu

Experiments with 5'-azacytidine and hematopoietic growth factor approved for the transformation of human mesenchymal cells into hematopoietic cells have demonstrated that cell fate can be dramatically altered by changing the epigenetic state of cells. Here, we demonstrate that umbilical cord-derived human mesenchymal stem cells (uMSC) are easily accessible and could be induced into cells with hematopoietic function. Furthermore, we focused on the crucial miRNAs and relative transcription factors (TFs) in our study. We show that combined Aza/GF incubation can increase expression of miR-218, miR-150, and miR-451. Accordingly, miR-218 overexpression achieved an increase in expression of CD34 (3-13%), CD45 (50-65%), CD133 and c-Kit in uMSCs that cultured with Aza/GF. The expression of the relevant transcriptional factors, such as HoxB4 and NF-Ya, was higher than in the negative control group or miR-218 inhibitor transfected group, and microphthalmia-associated transcription factor (MITF) is regarded to be a direct target of miR-218, as demonstrated by luciferase assays. Overexpression of miR-218 might, in conjunction with the MITF, upregulate the expression of NF-Ya and HoxB4, which induce a hematopoietic state. We concluded that miR-218 might have a role in the transformation of hematopoietic cells through the MITF pathway.