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心臓再生制御部

業績

心臓再生制御部では心筋細胞の若返りと増殖誘導機構の研究、心臓の再生における免疫細胞の役割、心臓発生を制御する遺伝子プログラムの研究、心血管系の発生とそのイメージングなど、広く心臓の発生と再生に関する基礎研究を推進して来ました。最近では企業との共同研究も開始し、新たな心臓の再生医療の開発を目指す応用研究も進めています。これまでに得られている研究成果のうち、主要なものを以下に示します。

主要な論文一覧

菊地部長

  1. Krüppel-like factor 1 is a core cardiomyogenic trigger in zebrafish. Ogawa M, Geng FS, Humphreys DT, Kristianto E, Sheng DZ, Hui SP, Zhang Y, Sugimoto K, Nakayama M, Zheng D, Hesselson D, Hodson MP, Bogdanovic O, Kikuchi K. Science 372:201-5 (2021)
  2. Zebrafish regulatory T cells mediate organ-specific regenerative programs. Hui SP, Sheng DZ, Sugimoto K, Gonzalez-Rajal A, Nakagawa S, Hesselson D, Kikuchi K. Dev Cell 43:659-672 (2017)
  3. Dissection of zebrafish shha function using site-specific targeting with a Cre-dependent genetic switch. Sugimoto K, Hui SP, Sheng DZ, Kikuchi K. eLife 6: e24635 (2017)
  4. Zebrafish FOXP3 is required for the maintenance of immune tolerance. Sugimoto K, Hui SP, Sheng DZ, Gonzalez-Rajal A, Nakayama M, Kikuchi K. Dev Comp Immunol 73:156-62 (2017)
  5. Cardiac regenerative capacity and mechanisms. Kikuchi K, Poss KD. Annu Rev Cell Dev Biol 28:719-741 (2012)
  6. tcf21+ epicardial cells adopt non-myocardial fates during zebrafish heart development and regeneration. Kikuchi K, Gupta V, Wang J, Holdway JE, Wills AA, Fang Y, Poss KD. Development 138:2895-2902 (2011)
  7. Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration. Kikuchi K, Holdway JE, Major RJ, Blum N, Dahn RD, Begemann G, Poss KD. Dev Cell 20:397-404 (2011)
  8. Primary contribution to zebrafish heart regeneration by gata4+ cardiomyocytes. Kikuchi K, Holdway JE, Werdich AA, Anderson RM, Fang Y, Egnaczyk GF, Evans T, Macrae CA, Stainier DYR, Poss KD. Nature 464:601-605 (2010)
  9. Developmental switch of mouse hematopoietic stem cells from fetal to adult type occurs in bone marrow after birth. Kikuchi K, Kondo M. Proc Natl Acad Sci USA 103:17852-17857 (2006)
  10. IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF. Kikuchi K, Lai AY, Hsu CL, Kondo M. J Exp Med 201: 1197-1203 (2005)

渡邉室長

  1. Watanabe Y *, Seya D, Ihara D, Ishii S, Uemoto T, Kubo A, Arai Y, Isomoto Y, Nakano A, Abe T, Shigeta M, Kawamura T, Saito Y, Ogura T, Nakagawa O*. (*Co-corresponding authors). Importance of endothelial Hey1 expression for thoracic great vessel development and its distal enhancer for Notch-dependent endothelial transcription. J Biol Chem 295:17632-17645 (2020)
  2. Ihara D, Watanabe Y *, Seya D, Arai Y, Isomoto Y, Nakano A, Kubo A, Ogura T, Kawamura T, Nakagawa O*. (*Co-corresponding authors). Expression of Hey2 transcription factor in the early embryonic ventricles is controlled through a distal enhancer by Tbx20 and Gata transcription factors. Dev Biol 461:124-131 (2020)
  3. Watanabe Y, Miyasaka KY, Kubo A, Kida YS, Nakagawa O, Hirate Y, Sasaki H, Ogura T. Notch and Hippo signaling converge on Strawberry Notch 1 (Sbno1) to synergistically activate Cdx2 during specification of the trophectoderm. Sci Rep 7:46135 (2017)
  4. Watanabe Y, Zaffran S, Kuroiwa A, Higuchi H, Ogura T, Harvey RP, Kelly RG, Buckingham M. Fgf10 regulation in the second heart field by Tbx1, Nkx2-5 and Islet1 reveals a genetic switch for down-regulation of transcription in the myocardium. Proc Natl Acad Sci U S A 109:18273-18280 (2012)
  5. Watanabe Y, Miyagawa-Tomita S, Vincent SD, Kelly RG, Moon AM, Buckingham M. Role of mesodermal FGF8 and FGF10 overlaps in the development of the arterial pole of the heart and pharyngeal arch arteries. Circ Res 106:495-503 (2010)
  6. Park EJ*, Watanabe Y *, Smyth G, Miyagawa-Tomita S, Meyers E, Klingensmith J, Camenisch T, Buckingham M, Moon AM. (*Co-first authors). An FGF autocrine loop initiated in second heart field mesoderm regulates morphogenesis at the arterial pole of the heart. Development 135:3599-3610 (2008)
  7. Watanabe Y *, Kokubo H*, Miyagawa-Tomita S, Endo M, Igarashi K, Aisaki K, Kanno J, Saga Y. (*Co-first authors). Activation of Notch1 signaling in cardiogenic mesoderm induces abnormal heart morphogenesis in mouse. Development 133:1625-1634 (2006)

安藤室長

  1. Ando K*, Tong L, Peng D, Vázquez-Liébanas E, Chiyoda H, He L, Liu J, Kawakami K, Mochizuki N, Fukuhara S, Grutzendler J, Betsholtz C*. (*Co-corresponding authors). KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling. Dev Cell doi: https://doi.org/10.1016/j.devcel.2022.04.019 (2022)
  2. Peng D, Ando K*, Gloger M, Skoczylas R, Mochizuki N, Betsholtz C, Fukuhara S, Koltowska K*. (*Co-corresponding authors). Proper migration of lymphatic endothelial cells requires survival and guidance cues from arterial mural cells. eLife 11:e74094 (2022)
  3. Ando K*, Ishii T., Fukuhara S. (*Corresponding author). Zebrafish vascular mural cell biology: recent advances, development, and functions. Life 11:1041 (2021)
  4. Ando K*, Shih YH, Ebarasi L, Grosse A, Portman D, Chiba A, Mattonet K, Gerrif C, Stainier DYR, Mochizuki N, Fukuhara S, Betsholtz C, Lawson ND*. (*Co-corresponding authors). Conserved and context-dependent roles for pdgfrb signaling during zebrafish vascular mural cell development. Dev Biol 479:11-22 (2021)
  5. Castro M, Laviña B, Ando K, Álvarez-Aznar A, Abu Taha A, Brakebusch C, Dejana E, Betsholtz C, Gaengel K. CDC42 deletion elicits cerebral vascular malformations via increased MEKK3-dependent KLF4 expression. Circ Res 124:1240-1252 (2019)
  6. Ando K*, Wang W, Peng D, Chiba A, Lagendijk A, Barske L, Crup JG, Stainier DYR, Lendahl U, Koltowska K, Hogan BM, Fukuhara S, Mochizuki N, Betsholtz C. (*Corresponding author). Periarterial specification of vascular mural cells from naïve mesenchyme requires Notch signaling. Development 146:dev165589 (2019)
  7. Vanlandewijck M, He L, Andaloussi Mäe M, Andrae J, Ando K, Del Gaudio F, Nahar K, Lebouvier T, Laviña B, Leonor Gouveia L, Raschperger E, Räsänen M, Zarb Y, Mochizuki N, Keller A, Lendahl U, Betsholtz C. A molecular atlas of cell types and zonation in the brain. Nature 554:475–480 (2018)
  8. Takara K, Eino D, Ando K, Yasuda D, Naito H, Tsukada Y, Iba T, Wakabayashi T, Muramatsu F, Kidoya H, Fukuhara S, Mochizuki N, Ishii S, Kishima H, Takakura N. Lysophosphatidic acid receptor 4 activation augments drug delivery in tumors by tightening endothelial cell-cell contact. Cell Rep 20:2072-2086 (2017)
  9. Ando K, Fukuhara S, Izumi N, Nakajima H, Fukui H, Kelsh RN, Mochizuki N. Clarification of mural cell coverage of vascular endothelial cells by live imaging of zebrafish. Development 143:1328-1339 (2016)
  10. Ando K, Fukuhara S, Moriya T, Obara Y, Nakahata N, Mochizuki N. Rap1potentiates endothelial cell junctions by spatially controlling myosin II activity and actin organization. J Cell Biol 202:901-916 (2013)

最終更新日:2022年05月31日

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