Mir-218 contributes to the transformation of 5-Aza/GF induced umbilical cord mesenchymal stem cells into hematopoietic cells through the MITF pathway.
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.
Research Center of Developmental Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
Kaimeng
K
Hu
Chen
C
Xu
Haitao
H
Ni
Zhenyu
Z
Xu
Yue
Y
Wang
Sha
S
Xu
Kaihong
K
Ji
Jun
J
Xiong
Houqi
H
Liu
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001374:Azacitidine / Q000494:pharmacology; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D044127:Epigenesis, Genetic; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D023081:CCAAT-Binding Factor; C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; C547471:MIRN218 microRNA, human; C497234:MITF protein, human; D035683:MicroRNAs; D051739:Microphthalmia-Associated Transcription Factor; C492061:NFYA protein, human; D019089:Stem Cell Factor; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D001374:Azacitidine