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First published online October 4, 2007
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2007-0490v1
26/1/202    most recent
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Submitted on June 20, 2007
Accepted on September 26, 2007

TISSUE-SPECIFIC STEM CELLS

Myocardin A Enhances Telomerase Activities in Adipose Tissue Mesenchymal Cells and Embryonic Stem Cells Undergoing Cardiovascular Myogenic Differentiation

Rosalinda Madonna 1, James T. Willerson 1, Yong-Jian Geng 1*

1 The University of Texas Health Science Center at Houston and the Texas Heart Institute, Houston, Texas 77030

* To whom correspondence should be addressed. E-mail: yong-jian.geng{at}uth.tmc.edu.


  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 a subpopulation of mesenchymal stem cells (MSCs) from adult adipose tissue, which co-express 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, TERT, at a level comparable to that of embryonic stem cells (ESCs). Both myocardin A and TERT could be co-immunoprecipitated from the developing MSCs and ESC-derived embryoid bodies (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.

Key Words. Stem cell, telomerase, myocardin, heart, development, myogenesis




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