earticle

영어

To establish induced pluripotent stem cell (iPSC) by reprogramming cells that is differentiated types, specific transcription factors are needed. Some researchers examined whether chemical molecules or proteins can replace transcription factors to alter the de fined cell fate. Previously, we confirmed that the treatment of bone morphogenetic protein 4 (BMP4) could intermediately reprogram the mouse skin fibroblasts (MSFs) to stem-like cells. In this study, to reprogram the cell more efficiently and definitely, we investigated the synergic effects of BMP4 and 4 kinds of small molecules, RG108, 5-azacytidine, Na-butyrate and PD173074, that regulates some signal transduction pathway. The ventral skin epidermis of an adult mouse were used to confirm the synergic reprogramming activity of small molecules. After the cells were cultured with BMP4, they were formed sphere-like organoid bodies (OBs) with BMP4 and each small molecules for 5 days. The activity of alkaline phosphatase was the highest in BMP4+RG108 group. Also, all the small molecule treated groups expressed high Oct-4 level than BMP4 treated group. To confirm the stem cell potency of these cells, we induced their differentiation into cardiomyocytes. The cells exhibited similar mRNA expression of cardiac mesoderm markers such as connexin 40 and GATA binding protein 4, and the cardiomyocyte marker troponin T among groups. However, the expression of one of the cardiac mesoderm marker gene, Nk2 transcription factor-related locus 5, was significantly decreased in BMP4+RG108 group. These results suggest that treatment of some small molecules may enhance the BMP4-mediated somatic stem cell reprogramming.