Do MSCs overexpressing Csx/Nkx2.5 and GATA4 accept the cardiomyogenic fate as unavoidable?

Do single cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4 accept the cardiomyogenic fate as unavoidable?

Bone marrow cells can give rise to cardiomyocytes as well as adipocytes, osteocytes, and chondrocytes in vitro. The existence of mesenchymal stem cells has been proposed, but it remains unclear if a single cell-derived stem cell stochastically committs toward a cardiac lineage. By single cell marking, we performed a follow-up study of individual cells during the differentiation of 9-15c mesenchymal cells derived from bone marrow cells. Three types of cells, i.e., cardiac myoblasts, cardiac progenitors and multipotent stem cells were differentiated from a single cell, implying that cardiomyocytes are generated stochastically from a single cell-derived stem cell. We also demonstrated that overexpression of Csx/Nkx2.5 and GATA4, precardiac mesodermal transcription factors, enhanced cardiomyogenic differentiation of 9-15c cells and frequency of the cardiomyogenic differentiation increased by co-culturing with fetal cardiomyocytes. Single cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4 behaved like a cardiac transient amplifying cell, and still retained their plasticity in vivo.