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Letters to Nature

Nature 433, 647-653 (10 February 2005) | doi:10.1038/nature03215; Received 12 October 2004; Accepted 22 November 2004

There is a Corrigendum (19 April 2007) associated with this document.

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Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages

Karl-Ludwig Laugwitz1,6, Alessandra Moretti1,6, Jason Lam1,6, Peter Gruber3, Yinhong Chen1, Sarah Woodard1, Li-Zhu Lin1, Chen-Leng Cai1, Min Min Lu4, Michael Reth5, Oleksandr Platoshyn2, Jason X.-J. Yuan2, Sylvia Evans1 & Kenneth R. Chien1

  1. Institute of Molecular Medicine and
  2. Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, California 92093, USA
  3. Children's Hospital of Philadelphia, Cardiac Center, Philadelphia, Pennsylvania 19104, USA
  4. Cardiovascular Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
  5. Max-Planck Institut für Immunbiologie, Universität Freiburg, Biologie III, Abteilung Molekulare Immunologie, Freiburg 79108, Germany
  6. These authors contributed equally to this work

Correspondence to: Sylvia Evans1Kenneth R. Chien1 Correspondence and requests for materials should be addressed to K.R.C. (Email: kchien@partners.org) or to S.E. (Email: syevans@ucsd.edu).

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The purification, renewal and differentiation of native cardiac progenitors would form a mechanistic underpinning for unravelling steps for cardiac cell lineage formation, and their links to forms of congenital and adult cardiac diseases1, 2, 3. Until now there has been little evidence for native cardiac precursor cells in the postnatal heart4. Herein, we report the identification of isl1+ cardiac progenitors in postnatal rat, mouse and human myocardium. A cardiac mesenchymal feeder layer allows renewal of the isolated progenitor cells with maintenance of their capability to adopt a fully differentiated cardiomyocyte phenotype. Tamoxifen-inducible Cre/lox technology enables selective marking of this progenitor cell population including its progeny, at a defined time, and purification to relative homogeneity. Co-culture studies with neonatal myocytes indicate that isl1+ cells represent authentic, endogenous cardiac progenitors (cardioblasts) that display highly efficient conversion to a mature cardiac phenotype with stable expression of myocytic markers (25%) in the absence of cell fusion, intact Ca2+-cycling, and the generation of action potentials. The discovery of native cardioblasts represents a genetically based system to identify steps in cardiac cell lineage formation and maturation in development and disease.

  1. Institute of Molecular Medicine and
  2. Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, California 92093, USA
  3. Children's Hospital of Philadelphia, Cardiac Center, Philadelphia, Pennsylvania 19104, USA
  4. Cardiovascular Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
  5. Max-Planck Institut für Immunbiologie, Universität Freiburg, Biologie III, Abteilung Molekulare Immunologie, Freiburg 79108, Germany
  6. These authors contributed equally to this work

Correspondence to: Sylvia Evans1Kenneth R. Chien1 Correspondence and requests for materials should be addressed to K.R.C. (Email: kchien@partners.org) or to S.E. (Email: syevans@ucsd.edu).