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Molecular Medicine |
From the Departments of Internal Medicine (A.M.M., T.D.G., D.J.G.) and Molecular Biology (E.N.O., D.J.G.), University of Texas Southwestern Medical Center, Dallas; Department of Oncology (C.A.W.), Presbyterian Hospital of Dallas, Texas; and Department of Medicine (R.S.W.), Duke University Medical Center, Durham, NC.
Correspondence to Daniel J. Garry, MD, PhD, NB11.118A 5323 Harry Hines Blvd, University of Texas Southwestern Medical Center Dallas, Dallas TX 75390-8573. E-mail daniel.garry{at}utsouthwestern.edu
Transcriptome-wide analysis of dynamically regulated progenitor cell populations has the potential to elucidate key aspects of cardiac development. The heart, as the first organ to develop in the mammal, is a technically challenging but clinically relevant target for study. To define the transcriptional program of the cardiac progenitor, we used a novel transgenic strategy and fluorescence-activated cell sorting to reliably label and isolate cardiac progenitors directly from mouse embryos. Pure populations of cardiac progenitor cells were isolated from the cardiac crescent and 2 subsequent stages of heart development: the linear heart tube and the looping heart. RNA was isolated from stage-specific cardiac progenitors and subjected to transcriptome analysis by oligonucleotide array hybridization. The cardiac transcriptional regulatory programs were compared with the molecular programs of age-matched noncardiac embryonic cells, embryonic stem cells, adult cardiomyocytes, and each other to identify sets of genes exhibiting differential expression in the cardiac progenitor cell population. These results define the transcriptional profile of mammalian cardiac progenitor cells and provide insight into the molecular regulation of the earliest periods of heart development.
Key Words: cardiac development gene array progenitor cells transcriptome transgenic mice
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