G Protein-Coupled Receptor APJ and Its Ligand Apelin Act Downstream of Cripto to Specify Embryonic Stem Cells Toward the Cardiac Lineage Through Extracellular Signal-Regulated Kinase/p70S6 Kinase Signaling Pathway

  • Cristina D'Aniello
    From the Stem Cell Fate Laboratory (C.D., E.L., S.I., O.G., G.M.), Institute of Genetics and Biophysics “A. Buzzati-Traverso,” Consiglio Nazionale delle Ricerche, Naples, Italy; Institute of Genetics and Biophysics “A. Buzzati-Traverso” (C.D., E.L., S.I., O.G., A.M.L., G.L.L., G.M.), Consiglio Nazionale delle Ricerche, Naples, Italy; Vesalius Research Center (M.A., P.C.), VIB, Leuven, Belgium; and Vesalius Research Center (P.C.), Katholieke Universiteit Leuven, Belgium.
  • Enza Lonardo
    From the Stem Cell Fate Laboratory (C.D., E.L., S.I., O.G., G.M.), Institute of Genetics and Biophysics “A. Buzzati-Traverso,” Consiglio Nazionale delle Ricerche, Naples, Italy; Institute of Genetics and Biophysics “A. Buzzati-Traverso” (C.D., E.L., S.I., O.G., A.M.L., G.L.L., G.M.), Consiglio Nazionale delle Ricerche, Naples, Italy; Vesalius Research Center (M.A., P.C.), VIB, Leuven, Belgium; and Vesalius Research Center (P.C.), Katholieke Universiteit Leuven, Belgium.
  • Salvatore Iaconis
    From the Stem Cell Fate Laboratory (C.D., E.L., S.I., O.G., G.M.), Institute of Genetics and Biophysics “A. Buzzati-Traverso,” Consiglio Nazionale delle Ricerche, Naples, Italy; Institute of Genetics and Biophysics “A. Buzzati-Traverso” (C.D., E.L., S.I., O.G., A.M.L., G.L.L., G.M.), Consiglio Nazionale delle Ricerche, Naples, Italy; Vesalius Research Center (M.A., P.C.), VIB, Leuven, Belgium; and Vesalius Research Center (P.C.), Katholieke Universiteit Leuven, Belgium.
  • Ombretta Guardiola
    From the Stem Cell Fate Laboratory (C.D., E.L., S.I., O.G., G.M.), Institute of Genetics and Biophysics “A. Buzzati-Traverso,” Consiglio Nazionale delle Ricerche, Naples, Italy; Institute of Genetics and Biophysics “A. Buzzati-Traverso” (C.D., E.L., S.I., O.G., A.M.L., G.L.L., G.M.), Consiglio Nazionale delle Ricerche, Naples, Italy; Vesalius Research Center (M.A., P.C.), VIB, Leuven, Belgium; and Vesalius Research Center (P.C.), Katholieke Universiteit Leuven, Belgium.
  • Anna Maria Liguoro
    From the Stem Cell Fate Laboratory (C.D., E.L., S.I., O.G., G.M.), Institute of Genetics and Biophysics “A. Buzzati-Traverso,” Consiglio Nazionale delle Ricerche, Naples, Italy; Institute of Genetics and Biophysics “A. Buzzati-Traverso” (C.D., E.L., S.I., O.G., A.M.L., G.L.L., G.M.), Consiglio Nazionale delle Ricerche, Naples, Italy; Vesalius Research Center (M.A., P.C.), VIB, Leuven, Belgium; and Vesalius Research Center (P.C.), Katholieke Universiteit Leuven, Belgium.
  • Giovanna L. Liguori
    From the Stem Cell Fate Laboratory (C.D., E.L., S.I., O.G., G.M.), Institute of Genetics and Biophysics “A. Buzzati-Traverso,” Consiglio Nazionale delle Ricerche, Naples, Italy; Institute of Genetics and Biophysics “A. Buzzati-Traverso” (C.D., E.L., S.I., O.G., A.M.L., G.L.L., G.M.), Consiglio Nazionale delle Ricerche, Naples, Italy; Vesalius Research Center (M.A., P.C.), VIB, Leuven, Belgium; and Vesalius Research Center (P.C.), Katholieke Universiteit Leuven, Belgium.
  • Monica Autiero
    From the Stem Cell Fate Laboratory (C.D., E.L., S.I., O.G., G.M.), Institute of Genetics and Biophysics “A. Buzzati-Traverso,” Consiglio Nazionale delle Ricerche, Naples, Italy; Institute of Genetics and Biophysics “A. Buzzati-Traverso” (C.D., E.L., S.I., O.G., A.M.L., G.L.L., G.M.), Consiglio Nazionale delle Ricerche, Naples, Italy; Vesalius Research Center (M.A., P.C.), VIB, Leuven, Belgium; and Vesalius Research Center (P.C.), Katholieke Universiteit Leuven, Belgium.
  • Peter Carmeliet
    From the Stem Cell Fate Laboratory (C.D., E.L., S.I., O.G., G.M.), Institute of Genetics and Biophysics “A. Buzzati-Traverso,” Consiglio Nazionale delle Ricerche, Naples, Italy; Institute of Genetics and Biophysics “A. Buzzati-Traverso” (C.D., E.L., S.I., O.G., A.M.L., G.L.L., G.M.), Consiglio Nazionale delle Ricerche, Naples, Italy; Vesalius Research Center (M.A., P.C.), VIB, Leuven, Belgium; and Vesalius Research Center (P.C.), Katholieke Universiteit Leuven, Belgium.
  • Gabriella Minchiotti
    From the Stem Cell Fate Laboratory (C.D., E.L., S.I., O.G., G.M.), Institute of Genetics and Biophysics “A. Buzzati-Traverso,” Consiglio Nazionale delle Ricerche, Naples, Italy; Institute of Genetics and Biophysics “A. Buzzati-Traverso” (C.D., E.L., S.I., O.G., A.M.L., G.L.L., G.M.), Consiglio Nazionale delle Ricerche, Naples, Italy; Vesalius Research Center (M.A., P.C.), VIB, Leuven, Belgium; and Vesalius Research Center (P.C.), Katholieke Universiteit Leuven, Belgium.

抄録

<jats:p> <jats:bold> <jats:italic>Rationale:</jats:italic> </jats:bold> Pluripotent stem cells represent a powerful model system to study the early steps of cardiac specification for which the molecular control is largely unknown. The EGF-CFC (epidermal growth factor-Cripto/FRL-1/Cryptic) Cripto protein is essential for cardiac myogenesis in embryonic stem cells (ESCs). </jats:p> <jats:p> <jats:bold> <jats:italic>Objective:</jats:italic> </jats:bold> Here, we study the role of apelin and its G protein-coupled receptor, APJ, as downstream targets of Cripto both in vivo and in ESC differentiation. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results:</jats:italic> </jats:bold> Gain-of-function experiments show that APJ suppresses neuronal differentiation and restores the cardiac program in Cripto <jats:sup>−/−</jats:sup> ESCs. Loss-of-function experiments point for a central role for APJ/apelin in the gene regulatory cascade promoting cardiac specification and differentiation in ESCs. Remarkably, we show for the first time that apelin promotes mammalian cardiomyogenesis via activation of mitogen-activated protein kinase/p70S6 through coupling to a Go/Gi protein. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions:</jats:italic> </jats:bold> Together our data provide evidence for a previously unrecognized function of APJ/apelin in the Cripto signaling pathway governing mesoderm patterning and cardiac specification in mammals. </jats:p>

収録刊行物

  • Circulation Research

    Circulation Research 105 (3), 231-238, 2009-07-31

    Ovid Technologies (Wolters Kluwer Health)

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