Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages

Karl Ludwig Laugwitz, Alessandra Moretti, Jason Lam, Peter Gruber, Yinhong Chen, Sarah Woodard, Li Zhu Lin, Chen Leng Cai, Min Min Lu, Michael Reth, Oleksandr Platoshyn, Jason Yuan, Sylvia Evans, Kenneth B. Chien

Research output: Contribution to journalArticle

1035 Citations (Scopus)

Abstract

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 diseases. Until now there has been little evidence for native cardiac precursor cells in the postnatal heart. 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. Coculture 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.

Original languageEnglish (US)
Pages (from-to)647-653
Number of pages7
JournalNature
Volume433
Issue number7026
DOIs
StatePublished - Feb 10 2005
Externally publishedYes

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Cell Lineage
Cardiac Myocytes
Stem Cells
Feeder Cells
Phenotype
Cell Fusion
Tamoxifen
Coculture Techniques
Muscle Cells
Action Potentials
Heart Diseases
Myocardium
Maintenance
Technology
Population

ASJC Scopus subject areas

  • General

Cite this

Laugwitz, K. L., Moretti, A., Lam, J., Gruber, P., Chen, Y., Woodard, S., ... Chien, K. B. (2005). Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature, 433(7026), 647-653. https://doi.org/10.1038/nature03215

Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. / Laugwitz, Karl Ludwig; Moretti, Alessandra; Lam, Jason; Gruber, Peter; Chen, Yinhong; Woodard, Sarah; Lin, Li Zhu; Cai, Chen Leng; Lu, Min Min; Reth, Michael; Platoshyn, Oleksandr; Yuan, Jason; Evans, Sylvia; Chien, Kenneth B.

In: Nature, Vol. 433, No. 7026, 10.02.2005, p. 647-653.

Research output: Contribution to journalArticle

Laugwitz, KL, Moretti, A, Lam, J, Gruber, P, Chen, Y, Woodard, S, Lin, LZ, Cai, CL, Lu, MM, Reth, M, Platoshyn, O, Yuan, J, Evans, S & Chien, KB 2005, 'Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages', Nature, vol. 433, no. 7026, pp. 647-653. https://doi.org/10.1038/nature03215
Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature. 2005 Feb 10;433(7026):647-653. https://doi.org/10.1038/nature03215
Laugwitz, Karl Ludwig ; Moretti, Alessandra ; Lam, Jason ; Gruber, Peter ; Chen, Yinhong ; Woodard, Sarah ; Lin, Li Zhu ; Cai, Chen Leng ; Lu, Min Min ; Reth, Michael ; Platoshyn, Oleksandr ; Yuan, Jason ; Evans, Sylvia ; Chien, Kenneth B. / Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. In: Nature. 2005 ; Vol. 433, No. 7026. pp. 647-653.
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