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Science 16 October 2009:
Vol. 326. no. 5951, pp. 426 - 429
DOI: 10.1126/science.1177350
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Reports

Generation of Functional Ventricular Heart Muscle from Mouse Ventricular Progenitor Cells

Ibrahim J. Domian,1,2,* Murali Chiravuri,1,* Peter van der Meer,1,3,* Adam W. Feinberg,4 Xi Shi,1 Ying Shao,1 Sean M. Wu,1,2 Kevin Kit Parker,2,4,5 Kenneth R. Chien1,2,6,{dagger}

The mammalian heart is formed from distinct sets of first and second heart field (FHF and SHF, respectively) progenitors. Although multipotent progenitors have previously been shown to give rise to cardiomyocytes, smooth muscle, and endothelial cells, the mechanism governing the generation of large numbers of differentiated progeny remains poorly understood. We have employed a two-colored fluorescent reporter system to isolate FHF and SHF progenitors from developing mouse embryos and embryonic stem cells. Genome-wide profiling of coding and noncoding transcripts revealed distinct molecular signatures of these progenitor populations. We further identify a committed ventricular progenitor cell in the Islet 1 lineage that is capable of limited in vitro expansion, differentiation, and assembly into functional ventricular muscle tissue, representing a combination of tissue engineering and stem cell biology.

1 Cardiovascular Research Center, Massachusetts General Hospital, Charles River Plaza, CPZN 3200, 185 Cambridge Street, Boston, MA 02114–2790, USA.
2 Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
3 Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, Netherlands.
4 Disease Biophysics Group, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
5 The Wyss Institue for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
6 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: krchien{at}partners.org

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