胚性幹細胞を用いた高率心筋細胞誘導法の開発

• Project/Area Number: 18790513
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Keio University
• Principal Investigator: 湯浅 慎介 Keio University, 医学部, 助教 (90398628)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: 胚性幹細胞 / 心筋細胞 / 分化誘導

Research Abstract

胚性幹細胞(Embryonic Stem Cell(ES細胞))からの分化誘導は、生理的状況下における発生において重要な因子が同様に関与していると考えられている。そこで我々は、過去に心臓発生に重要とされる因子を検討したが、充分な効果は得られなかった。発生学的観点から見直したところBMP antagonistであるNogginが心臓発生領域で発現し、Nogginを胚性幹細胞に作用させると高率に心筋細胞を誘導できることを見いだした(Yuasa S, et. al. Transient inhibition of BMP signaling by Noggin induces cardiomyocyte diflferentiation of mouse embryonic stem cells. Nature Biotechnology. 2005 May; 23(5):607-611.)。さらなる分化誘導効率の上昇を目的として、発生学的に重要な他の因子も検討していたところ、現在までに数種類の遺伝子(分泌因子)が心臓発生予定領域に発現し、かっ胚性幹細胞の分化誘導効率を上昇させることが判明した。現在は、一つの因子に注目して解析中である。その因子のレセプターは、心臓発生の胎生中期に非常に強く発現している。その因子を胎仔に注射すると胎仔の心筋細胞が増殖することが確認され、新規心筋細胞増殖因子であることが判明した。また、その因子を分化途中のES細胞に添加することにより、心筋細胞を増殖することが判明した。

Research Products

• [Journal Article] Common marmoset embryonic stem cell can differentiate into cardiomyocytes. (2008)
  • Author(s): Chen H, Hattori F, Murata M, Li W, Yuasa S, Onizuka T, Shimoji K, Ohno y Sasaki E, Kimura K, Hakuno D, Sano M, Makino S, Ogawa S, Fukuda K.
  • Journal Title: Biochem Biophys Res Commun. 9;369(3) Pages: 801-806
  • Peer Reviewed
• [Journal Article] Dominant negative suppression of Rad leads to QT prolongation andcauses ventricular arrhythmias via modulation of L-type Ca2+channels in the heart. (2007)
  • Author(s): Yada H, Murata M, ShimodaK, Yuasa S, Kawaguchi H, leda M, Adachi T, Murata M, 0gawa S, Fukuda K.
  • Journal Title: Circulation Research 6;101(1) Pages: 69-77
  • Peer Reviewed
• [Journal Article] Bone Marrow Derived Cells Are Involved in the Pathogenesis of Cardiac Hypertrophy in Response to Pressure Overload. (2007)
  • Author(s): Endo J, Sano M, Fujita J, Hayashida K, Yuasa S, Aoyama N, Takehara Y, Kato 0, Makino S, Ogawa S, Fukuda K.
  • Journal Title: Circulation 116(10):11 Pages: 76-84
  • Peer Reviewed
• [Journal Article] Administration of Granulocyte Colony-Stimulating Factor after Myocardial Infarction Enhances the Recruitment of Hematopoietic Stem Cell-Derived Myofibroblasts and Contributes to Cardiac Repair. (2007)
  • Author(s): Fujita J, Mori M, Kawada H, leda Y, Tsuma M, Matsuzaki Y, Kawaguchi H, Yagi T, Yuasa J, Endo J, Hotta T, Ogawa S, Okano H, Yozu R, Ando K, Fukuda K.
  • Journal Title: Stem Cells. 25(11) Pages: 2750-2759
  • Peer Reviewed
• [Journal Article] Intramolecular Control 0f Protein stability, Subnuclear Compartmentalization, and Coactivator Function of Peroxisome Proliferator-activatedReceptor γ Coactivator 1α. (2007)
  • Author(s): Sano M, Tokudome S, ShimizuN, Yoshikawa N, Ogawa C, Shirakawa K, Endo J, Katayama T, Yuasa S, Ieda M, Makino S, Hattori F, Tanaka H, Fukuda K.
  • Journal Title: J Biol Chem. 282(35) Pages: 25970-25980
  • Peer Reviewed
• [Journal Article] Stem cells as a source of regenerative cardiomyocytes. (2006)
  • Author(s): Fukuda K, Yuasa S.
  • Journal Title: Circulation Research 28;98(8) Pages: 1002-1013
• [Journal Article] Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis. (2006)
  • Author(s): Yoshioka M, Yuasa S, Matsumura K, et al.
  • Journal Title: Nature Medicine. 12(10) Pages: 1151-1159
  • NAID: 10017243402
• [Journal Article] E-Cadherin-Coated Plates Maintain Pluripotent ES Cells without Colony Formation. (2006)
  • Author(s): Nagaoka M, Koshimizu U, Yuasa S, et al.
  • Journal Title: PLoS ONE. Dec 20・1
• [Presentation] Cardiomyocyte differentiation in vitro and in vivo (2008)
  • Author(s): Yuasa S, et. al.
  • Organizer: The Japanese Circulation Society
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2008-03-29
• [Presentation] Zacl is an essential cardiac transcription factor (2008)
  • Author(s): Yuasa S, et. al.
  • Organizer: The Japanese Circulation Society
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2008-03-28
• [Presentation] Zacl is an essential cardiac transcription factor (2008)
  • Author(s): Yuasa S, et. al.
  • Organizer: Keystone Symposia
  • Place of Presentation: Colorado, America
  • Year and Date: 2008-01-16
• [Presentation] The Novel BTB/POZ Protein, RhoBTB3, Regulates Mitochondrial Function Via The Ubiquitin Proteasome System (2007)
  • Author(s): Yuasa S, et. al.
  • Organizer: American Heart Association
  • Place of Presentation: Or1and, America
  • Year and Date: 2007-11-06
• [Presentation] Zac l is an essential cardiac transcription factor (2007)
  • Author(s): Yuasa S, et. a1.
  • Organizer: American Heart Association
  • Place of Presentation: Or1and, America
  • Year and Date: 2007-11-05