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BAS/BSCR poster abstract
BAS/BSCR36 Regulation of human smooth muscle cell development by myocardin
  1. L Raphel,
  2. S Sinha
  1. Division of Cardiovascular Medicine, University of Cambridge, UK

Abstract

Background Myocardin is a cardiac-specific and smooth muscle cell (SMC)-specific transcription factor with a key role in development. It regulates a wide variety of SMC-specific contractile markers by acting as an accessory protein for serum response factor, binding to its DNA binding sites (CArG boxes), and so has a major effect on SMC phenotype. However, its precise role in SMC development remains unclear. Moreover, there are no data on its requirement in human SMC development.

Methodology We investigated whether myocardin was required for SMC development from human embryonic stem cells in an embryoid body model and whether we could promote SMC development at high efficiency by overexpressing myocardin.

Results & conclusions Embryoid bodies from human embryonic stem cells were found to express increasing quantities of SMC markers up to 60 days of development with the appearance of visibly contractile SMC patches as a late phenomenon. Overexpression of myocardin using an adenovirus vector increased differentiation of pluripotent cells into the SMC lineage, although only a subset of cells was susceptible to the overexpressed transcription factor. Loss of function studies using a truncated myocardin dominant negative construct resulted in only minor or no reduction in SMC differentiation, suggesting that redundant pathways exist during embryonic development in human cells.

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