Myocardin a enhances telomerase activities in adipose tissue mesenchymal cells and embryonic stem cells undergoing cardiovascular myogenic differentiation

Abstract

Acting as a reverse transcriptase that maintains nuclear telomere length and replication potential, telomerase usually decreases in expression and activities when mammalian stem cells undergo terminal differentiation. This study identified, in adult adipose tissue, a subpopulation of mesenchymal stem cells (MSCs) that coexpresses telomerase and myocardin A, a key regulator of cardiovascular myogenic development. The telomerase/myocardin A-positive MSCs differentiated into cardiovascular myogenic cells while retaining expression and activation of the telomerase catalytic unit, telomerase reverse transcriptase (TERT), at a level comparable to that of ESCs. Both myocardin A and TERT could be coimmunoprecipitated from the developing MSCs and ESC-derived EBs with either anti-TERT or anti-myocardin A antibodies, suggesting the formation of TERT-myocardin A complexes in the MSCs and EBs. The proteins pulled down with anti-myocardin antibodies showed almost the same levels of telomerase activities as those precipitated with anti-TERT antibodies. Overexpression of myocardin A by cDNA transfection significantly increased telomerase activities and promoted telomere synthesis by MSCs. The data from this study indicate a potentially novel function of myocardin A in maintaining the myogenic stemness in developing MSCs and EBs by enhancing telomerase activation and promoting myogenic gene expression.