Access

Letter

Nature 459, 708-711 (4 June 2009) | doi:10.1038/nature08039; Received 6 March 2009; Accepted 7 April 2009; Published online 26 April 2009

Open Innovation Challenges

naturejobs

Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors

Jun K. Takeuchi1,2 & Benoit G. Bruneau1,3

  1. Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA
  2. Division of Cardiovascular Research, Global-Edge Institute, Tokyo Institute of Technology, Frontier S2-16, Nagatsuda, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
  3. Department of Pediatrics, Cardiovascular Research Institute, and Institute for Regeneration Medicine, University of California, San Francisco, California 94158, USA

Correspondence to: Jun K. Takeuchi1,2Benoit G. Bruneau1,3 Correspondence and requests for materials should be addressed to B.G.B. (Email: bbruneau@gladstone.ucsf.edu) or J.K.T. (Email: takeuchi.j.ab@m.titech.ac.jp).

Top

Heart disease is the leading cause of mortality and morbidity in the western world. The heart has little regenerative capacity after damage, leading to much interest in understanding the factors required to produce new cardiac myocytes. Despite a robust understanding of the molecular networks regulating cardiac differentiation1, 2, no single transcription factor or combination of factors has been shown to activate the cardiac gene program de novo in mammalian cells or tissues. Here we define the minimal requirements for transdifferentiation of mouse mesoderm to cardiac myocytes. We show that two cardiac transcription factors, Gata4 and Tbx5, and a cardiac-specific subunit of BAF chromatin-remodelling complexes, Baf60c (also called Smarcd3), can direct ectopic differentiation of mouse mesoderm into beating cardiomyocytes, including the normally non-cardiogenic posterior mesoderm and the extraembryonic mesoderm of the amnion. Gata4 with Baf60c initiated ectopic cardiac gene expression. Addition of Tbx5 allowed differentiation into contracting cardiomyocytes and repression of non-cardiac mesodermal genes. Baf60c was essential for the ectopic cardiogenic activity of Gata4 and Tbx5, partly by permitting binding of Gata4 to cardiac genes, indicating a novel instructive role for BAF complexes in tissue-specific regulation. The combined function of these factors establishes a robust mechanism for controlling cellular differentiation, and may allow reprogramming of new cardiomyocytes for regenerative purposes.

  1. Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA
  2. Division of Cardiovascular Research, Global-Edge Institute, Tokyo Institute of Technology, Frontier S2-16, Nagatsuda, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
  3. Department of Pediatrics, Cardiovascular Research Institute, and Institute for Regeneration Medicine, University of California, San Francisco, California 94158, USA

Correspondence to: Jun K. Takeuchi1,2Benoit G. Bruneau1,3 Correspondence and requests for materials should be addressed to B.G.B. (Email: bbruneau@gladstone.ucsf.edu) or J.K.T. (Email: takeuchi.j.ab@m.titech.ac.jp).

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NEWS AND VIEWS

How does the mouse get its trunk?

Nature Genetics News and Views (01 Apr 2001)

Developmental biology The early heart remodelled

Nature News and Views (04 Jun 2009)