Akiko Nakano

Publications (2)12.08 Total impact

• Article: Adrenomedullin/cyclic AMP pathway induces Notch activation and differentiation of arterial endothelial cells from vascular progenitors.

  Takami Yurugi-Kobayashi, Hiroshi Itoh, Timm Schroeder, Akiko Nakano, Genta Narazaki, Fumiyo Kita, Kentoku Yanagi, Mina Hiraoka-Kanie, Emi Inoue, Toshiaki Ara, Takashi Nagasawa, Ursula Just, Kazuwa Nakao, Shin-ichi Nishikawa, Jun K Yamashita
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  ABSTRACT: The acquisition of arterial or venous identity is highlighted in vascular development. Previously, we have reported an embryonic stem (ES) cell differentiation system that exhibits early vascular development using vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2)-positive cells as common vascular progenitors. In this study, we constructively induced differentiation of arterial and venous endothelial cells (ECs) in vitro to elucidate molecular mechanisms of arterial-venous specification. ECs were induced from VEGFR2+ progenitor cells with various conditions. VEGF was essential to induce ECs. Addition of 8bromo-cAMP or adrenomedullin (AM), an endogenous ligand-elevating cAMP, enhanced VEGF-induced EC differentiation. Whereas VEGF alone mainly induced venous ECs, 8bromo-cAMP (or AM) with VEGF supported substantial induction of arterial ECs. Stimulation of cAMP pathway induced Notch signal activation in ECs. The arterializing effect of VEGF and cAMP was abolished in recombination recognition sequence binding protein at the Jkappa site deficient ES cells lacking Notch signal activation or in ES cells treated with gamma-secretase inhibitor. Nevertheless, forced Notch activation by the constitutively active Notch1 alone did not induce arterial ECs. Adrenomedullin/cAMP is a novel signaling pathway to activate Notch signaling in differentiating ECs. Coordinated signaling of VEGF, Notch, and cAMP is required to induce arterial ECs from vascular progenitors.
  Arteriosclerosis Thrombosis and Vascular Biology 10/2006; 26(9):1977-84. · 6.37 Impact Factor
• Article: Prospective identification of cardiac progenitors by a novel single cell-based cardiomyocyte induction.

  Jun K Yamashita, Makoto Takano, Mina Hiraoka-Kanie, Chikashi Shimazu, Yan Peishi, Kentoku Yanagi, Akiko Nakano, Emi Inoue, Fumiyo Kita, Shin-Ichi Nishikawa
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  ABSTRACT: Dissection of cardiomyocyte differentiation process at the cellular level is indispensable in the research for cardiac development and regeneration. Previously, we have established an embryonic stem cell differentiation system that reproduces early vascular development from progenitor cells that express Flk1, a vascular endothelial growth factor receptor, by the combinatory application of 2-dimensional culture and flowcytometry. Here we show that cardiomyocytes can be successfully induced from a single Flk1+ cell on 2-dimensional culture, enabling the direct observation of differentiating cardiomyocytes and the prospective identification of cardiac progenitor potentials. Flk1+ cells could give rise to cardiomyocytes, as well as endothelial cells, from a single cell by the co-culture on OP9 stroma cells in a fusion-independent manner. Among the cell populations in intermediate stages from Flk1+ cells to cardiomyocytes, Flk1+/CXCR4+/vascular endothelial cadherin- cells were cardiac-specific progenitors at the single cell level. Noggin, a bone morphogenetic protein inhibitor, abolished cardiomyocyte differentiation by inhibiting the cardiac progenitor induction. However, wnt inhibitors Dkk-1 or Frizzled-8/Fc chimeric protein augmented, but wnt3a inhibited, cardiomyocyte differentiation. In vitro reproduction of cardiomyocyte differentiation process should be a potent tool for the cellular and molecular elucidation of cardiac development, which would provide various targets for cardiac regeneration.
  The FASEB Journal 10/2005; 19(11):1534-6. · 5.71 Impact Factor