Overexpression of the c-Myb but not its leukemogenic mutant DNA-binding domain increased adipogenic differentiation in mesenchymal stem cells

The c-Myb protein is a vital transcription factor that regulates the differentiation of hematopoietic cells. Previous works have noticed that c-Myb is involved in an epigenetic control mechanism, in which the c-Myb DNA-binding domain (DBD) binds to the N-terminal histone tail of H3 to facilitate it acetylation and activate endogenous differentiation genes, while the leukemogenic mutant of c-Myb does not have these functions. However, whether c-Myb has corresponding biologic functions on the differentiation of other cells except for hematopoietic cells has not been explored. In our studies, we constructed the c-Myb wild type and its leukemogenic mutant DBD recombinant adenovirus with replication-defective adenoviral vectors carrying the GFP gene. We compared their roles on adipogenic differentiation efficiency in human bone marrow-derived mesenchymal stem cells (hMSCs). Our results demonstrated that the overexpression of c-Myb could enhance adipogenic differentiation in hMSCs, while the overexpression of its leukemogenic mutant blocked the adipogenic differentiation to a certain extent. These suggest that c-Myb play an important role in the hMSCs differentiation too, which is consistent with the epigenetic control mechanism of c-Myb.

► We observed the lipid formation course in the hMSCs highly expressing c-Myb and its leukemogenic mutants DBD recombinant adenovirus under fluorescence microscopy. ► Overexpression of c-Myb resulted in more cells to differentiate into adipocytes, while the overexpression of its leukemogenic mutants led to sharp decrease of cells differentiating into adipocytes. ► The mRNA level of PPARγ2 was enhanced significantly in hMSCs overexpressing c-Myb wild type, but decreased in cells overexpressing the leukemogenic mutants.