Functional characterization of cardiac progenitor cells and their derivatives in the embryonic heart post‐chamber formation |
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Authors: | Nichole M. McMullen Feixiong Zhang Adam Hotchkiss Frederic Bretzner Jennifer M. Wilson Hong Ma Karim Wafa Robert M. Brownstone Kishore B.S. Pasumarthi |
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Affiliation: | 1. Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada;2. Department of Anatomy and Neurobiology and Neuroscience Institute, Dalhousie University, Halifax, Nova Scotia, Canada;3. Department of Surgery (Neurosurgery), Dalhousie University, Halifax, Nova Scotia, Canada |
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Abstract: | There is scant information on the fate of cardiac progenitor cells (CPC) in the embryonic heart after chamber specification. Here we simultaneously tracked three lineage‐specific markers (Nkx2.5, MLC2v, and ANF) and confirmed that CPCs with an Nkx2.5+MLC2v?ANF? phenotype are present in the embryonic (E) day 11.5 mouse ventricular myocardium. We demonstrated that these CPCs could give rise to working cardiomyocytes and conduction system cells. Using a two‐photon imaging analysis, we found that the majority of CPCs are not capable of developing Ca2+ transients in response to β‐adrenergic receptor stimulation. In contrast, Nkx2.5+ cells expressing MLC2v but not ANF are capable of developing functional Ca2+ transients. We showed that Ca2+ transients could be invoked in Nkx2.5+MLC2v+ANF+ cells only upon inhibition of Gi, muscarinic receptors, or nitric oxide synthase (NOS) signaling pathways. Our data suggest that these inhibitory pathways may delay functional specification in a subset of developing ventricular cells. Developmental Dynamics 238:2787–2799, 2009. © 2009 Wiley‐Liss, Inc. |
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