Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antigens, CD / genetics
-
Antigens, CD / metabolism
-
Azacitidine / pharmacology
-
CCAAT-Binding Factor / genetics
-
CCAAT-Binding Factor / metabolism
-
Cell Differentiation / drug effects
-
Epigenesis, Genetic
-
Fetal Blood / cytology*
-
Fetal Blood / drug effects
-
Fetal Blood / metabolism
-
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
-
Hematopoietic Stem Cells / cytology*
-
Hematopoietic Stem Cells / drug effects
-
Hematopoietic Stem Cells / metabolism
-
Homeodomain Proteins / genetics
-
Homeodomain Proteins / metabolism
-
Humans
-
Mesenchymal Stem Cells / cytology*
-
Mesenchymal Stem Cells / drug effects
-
Mesenchymal Stem Cells / metabolism
-
MicroRNAs / genetics*
-
MicroRNAs / metabolism
-
Microphthalmia-Associated Transcription Factor / genetics*
-
Microphthalmia-Associated Transcription Factor / metabolism
-
Proto-Oncogene Proteins c-kit / genetics
-
Proto-Oncogene Proteins c-kit / metabolism
-
Signal Transduction
-
Stem Cell Factor / pharmacology
-
Transcription Factors / genetics
-
Transcription Factors / metabolism
Substances
-
Antigens, CD
-
CCAAT-Binding Factor
-
HOXB4 protein, human
-
Homeodomain Proteins
-
MIRN218 microRNA, human
-
MITF protein, human
-
MicroRNAs
-
Microphthalmia-Associated Transcription Factor
-
NFYA protein, human
-
Stem Cell Factor
-
Transcription Factors
-
Granulocyte-Macrophage Colony-Stimulating Factor
-
Proto-Oncogene Proteins c-kit
-
Azacitidine