Elucidation of the target genes for the treatment of lipid disorder by gene-trap method in human haploid cells

• Project/Area Number: 23659469
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kyoto University
• Principal Investigator: ONO Koh 京都大学, 医学研究科, 講師 (00359275)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 遺伝子トラップ / ハプロイド / マイクロ RNA / マイクロRNA / ハプロイド細胞

Research Abstract

We have developed gene-trap method and applied it to adipocyte differentiation. However, mammalian cells are diploid and only such genes which have haploid insufficiency can be obtained by this method. This time we utilized P1-55 cells, which is a human haploid cell line, and enabled to screen all genes by gene-trap method.

Research Products

• [Journal Article] Metastasis-associated protein, S100A4 mediates cardiac fibrosis potentially through the modulation of p53 in cardiac fibroblasts (2013)
  • Author(s): Tamaki Y, Iwanaga Y, Niizuma S, Kawashima T, Kato T, Inuzuka Y, Horie T, Morooka H, Takase T, Akahashi Y, Kobuke K, Ono K, Shioi T, Sheikh SP, Ambartsumian N, Lukanidin E, Koshimizu TA, Miyazaki S, Kimura T.
  • Journal Title: J Mol Cell Cardiol Volume: 57 Pages: 72-81
  • Peer Reviewed
• [Journal Article] Metastasis-associated protein, S100A4 mediates cardiac fibrosis potentially through the modulation of p53 in cardiac fibroblasts (2013)
  • Author(s): Tamaki Y, Iwanaga Y, Niizuma S, Kawashima T, Kato T, Inuzuka Y, Horie T, Morooka H, Takase T, Akahashi Y, Kobuke K, Ono K, Shioi T, Sheikh SP, Ambartsumian N, Lukanidin E, Koshimizu TA, Miyazaki S, Kimura T
  • Journal Title: J Mol Cell Cardiol Volume: 57 Pages: 72-81
  • DOI: 10.1016/j.yjmcc.2013.01.007
  • Peer Reviewed
• [Journal Article] MicroRNA-33-deficiency reduces the progression of atherosclerotic plaque in apoE-/- mice (2012)
  • Author(s): Horie T, Baba O, Kuwabara Y, Chujo Y, Watanabe S, Kinoshita M, Horiguchi M, Nakamura T, Chonabayashi K, Hishizawa M, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K.
  • Journal Title: J Am Heart Assoc Volume: 1
  • Peer Reviewed
• [Journal Article] Current concept of reverse cholesterol transport and novel strategy for atheroprotection. (2012)
  • Author(s): Ono K
  • Journal Title: J Cardiol. Volume: 60 Pages: 339-43
  • NAID: 120004996385
  • Peer Reviewed
• [Journal Article] Highly Purified Eicosapentaenoic Acid Increases Interleukin-10 Levels of Peripheral Blood Monocytes in Obese Patients With Dyslipidemia (2012)
  • Author(s): Satoh-Asahara N, Shimatsu A, Sasaki Y, Nakaoka H, Himeno A, Tochiya M, Kono S, Takaya T, Ono K, Wada H, Suganami T, Hasegawa K, Ogawa Y
  • Journal Title: Diabetes Care Volume: 35 Pages: 2631-9
  • Peer Reviewed
• [Journal Article] MicroRNA 26b Encoded by the Intron of Small CTD Phosphatase (SCP) 1 Has an Antagonistic Effect on its Host Gene. (2012)
  • Author(s): Sowa N, Horie T, Kuwabara Y, Baba O, Watanabe S, Nishi H, Kinoshita M, Takanabe-Mori R, Wada H, Shimatsu A, Hasegawa K, Kimura T, and Ono K
  • Journal Title: Journal of Cellular Biochem Volume: 113 Pages: 3455-65
  • Peer Reviewed
• [Journal Article] α1-Antitrypsin-low-density-lipoprotein Serves as a Marker of Smoking-specific Oxidative Stress (2012)
  • Author(s): Wada H, Ura S, Satoh-Asahara N, Kitaoka S, Mashiba S, Akao M, Abe M, Ono K, Morimoto T, Fujita M, Shimatsu A, Takahashi Y, Hasegawa K.
  • Journal Title: J Atheroscler Thromb Volume: 19 Pages: 47-58
  • Peer Reviewed
• [Journal Article] MicroRNA-33-deficiency reduces the progression of atherosclerotic plaque in apoE-/- mice (2012)
  • Author(s): Horie T, Baba O, Kuwabara Y, Chujo Y, Watanabe S, Kinoshita M, Horiguchi M, Nakamura T, Chonabayashi K, Hishizawa M, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K
  • Journal Title: JAm Heart Assoc Volume: 1 Issue: 6
  • DOI: 10.1161/jaha.112.003376
  • Peer Reviewed
• [Journal Article] Highly purified eicosapentaenoic acid increases interleukin-10 levels of peripheral blood monocytes in obese patients with dyslipidemia (2012)
  • Author(s): N. Satoh-Asahara, A. Shimatsu, Y. Sasaki, H. Nakaoka, A. Himeno, M. Tochiya, S. Kono, T. Takaya, K. Ono, H. Wada, T. Suganami, K. Hasegawa, Y. Ogawa
  • Journal Title: Diabetes Care Volume: 35 Issue: 12 Pages: 2631-2639
  • DOI: 10.2337/dc12-0269
  • Peer Reviewed
• [Journal Article] MicroRNA 26b Encoded by the Intron of Small CTD Phosphatase (SCP) 1 Has an Antagonistic Effect on its Host Gene (2012)
  • Author(s): Sowa N, Horie T, Kuwabara Y, Baba O, Watanabe S, Nishi H, Kinoshita M, Takanabe-Mori R, Wada H, Shimatsu A, Hasegawa K, Kimura T, and Ono K
  • Journal Title: Journal ofCellular Biochem. Volume: 113 Issue: 11 Pages: 3455-65
  • DOI: 10.1002/jcb.24222
  • Peer Reviewed
• [Journal Article] α1-Antitrypsin-low-density-lipoprotein Serves as a Marker of Smoking-specific Oxidative Stress. (2012)
  • Author(s): Wada-H
  • Journal Title: J Atheroscler Thromb Volume: 19 Pages: 47-58
  • Peer Reviewed
• [Journal Article] Increased microRNA-1 and microRNA-133a Levels in Serum of Patients with Cardiovascular Disease Indicate the Existence of Myocardial Damage (2011)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S, Imai M, Tamura T, Kita T, Kimura T.
  • Journal Title: Circulation: Cardiovascular Genetics Volume: 4 Pages: 446-454
  • Peer Reviewed
• [Journal Article] MicroRNA links obesity and impaired glucose metabolism (2011)
  • Author(s): Ono K
  • Journal Title: Cell Res Volume: 21 Pages: 864-6
  • NAID: 120004225541
  • Peer Reviewed
• [Journal Article] MicroRNAs and Cardiovascular Diseases (2011)
  • Author(s): Ono K, Kuwabara Y, Han J
  • Journal Title: FEBS J Volume: 278 Pages: 1619-33
  • NAID: 40020456062
  • Peer Reviewed
• [Journal Article] MicroRNA-27a regulates beta cardiac myosin heavy chain gene expression by targeting thyroid hormone receptor beta 1 in neonatal rat ventricular myocytes (2011)
  • Author(s): Nishi H, Ono K, Horie T, Nagao K, Kinoshita M, Kuwabara Y, Watanabe S, Takaya T, Tamaki Y, Takanabe-Mori R, Wada H, Hasegawa K, Iwanaga Y, Kawamura T, Kita T, Kimura T
  • Journal Title: Mol Cell Biol Volume: 31 Pages: 44-45
  • NAID: 120002871162
  • Peer Reviewed
• [Journal Article] miRNA-33 は生体内でコレステロールを制御する (2011)
  • Author(s): 尾野 亘、堀江貴裕、木村 剛、北 徹
  • Journal Title: 実験医学 Volume: 29 Pages: 575-578
• [Journal Article] マイクロ RNA と循環器疾患 (2011)
  • Author(s): 尾野 亘
  • Journal Title: 最新医学 Volume: 66 Pages: 2580-2586
• [Journal Article] Increased microRNA-1 and microRNA-133a Levels in Serum of Patients with Cardiovascular Disease Indicate the Existence of Myocardial Damage. (2011)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S, Imai M, Tamura T, Kita T, Kimura T.
  • Journal Title: Circulation: Cardiovascular Genetics. Volume: 4 Pages: 446-454
  • Peer Reviewed
• [Journal Article] MicroRNA links obesity and impaired glucose metabolism. (2011)
  • Author(s): Ono K.
  • Journal Title: Cell Res. Volume: 21 Pages: 864-866
  • NAID: 120004225541
• [Journal Article] MicroRNAs and Cardiovascular Diseases. (2011)
  • Author(s): Ono K, Kuwabara Y, Han J.
  • Journal Title: FEBS J Volume: 278 Pages: 1619-1633
  • NAID: 40020456062
  • Peer Reviewed
• [Journal Article] MicroRNA-27a regulates beta cardiac myosin heavy chain gene expression by targeting thyroid hormone receptor beta 1 in neonatal rat ventricular myocytes. (2011)
  • Author(s): Nishi H, Ono K, Horie T, Nagao K, Kinoshita M, Kuwabara Y, Watanabe S, Takaya T, Tamaki Y, Takanabe-Mori R, Wada H, Hasegawa K, Iwanaga Y, Kawamura T, Kita T, Kimura T.
  • Journal Title: Mol Cell Biol. Volume: 31 Pages: 744-755
  • NAID: 120002871162
  • Peer Reviewed
• [Journal Article] 実験医学 (2011)
  • Author(s): 尾野 亘、堀江貴裕、木村 剛、北 徹
  • Journal Title: miRNA-33は生体内でHDLコレステロールを制御する Volume: 29 Pages: 575-578
• [Journal Article] 最新医学 (2011)
  • Author(s): 尾野 亘
  • Journal Title: マイクロRNAと循環器疾患 Volume: 66 Pages: 2580-2586
• [Presentation] Symposium 6 (Insulin resistance) MicroRNA regulation of lipid homeostasis. (2012)
  • Author(s): Ono K
  • Organizer: 25th Spring Congress of Korean Diabetes Association
  • Place of Presentation: Hotel Inter-Burgo Exco, Daegu(Korea)
  • Year and Date: 2012-05-11
• [Presentation] MicroRNA-33-deficiency reduces the progression of atherosclerotic plaque in apoE-/- mice (2012)
  • Author(s): Ono K
  • Organizer: Cold spring harbor laboratory meeting. Regulatory and non-coding RNA
  • Place of Presentation: NY, U.S.A
• [Presentation] MicroRNA 33 Deficiency Reduces Atherosclerotic Plaque progression in ApoE Knockout Mice (2012)
  • Author(s): Baba O, Horie T, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, and Ono K.
  • Organizer: European Society of Cardiology Congress
  • Place of Presentation: Munich(Germany)
• [Presentation] Interaction of S100A4 with p53 in fibroblasts modulates cardiac fibrosis through two distinct mechanisms. (2012)
  • Author(s): Tamaki Y, Iwanaga Y, Ono K, Shioi T, Sheikh SP, Ambartsumian N, Lukanidin E, Koshimizu T, Miyazaki S, Kimura T
  • Organizer: European Society of Cardiology Congress
  • Place of Presentation: Munich(Germany)
• [Presentation] MicroRNA 33 Deficiency in Leukocytes Reduced the Lipid Accumulation in Atherosclerotic Plaque in ApoE Knockout Mice (2012)
  • Author(s): Baba O, Horie T, Kuwabara Y, Izuhara M, Usami S, Nakao T, Nishiga M, Nishino T, Sowa N, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, and Ono K
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Los Angeles Convention Center Los Angeles(U.S.A.)
• [Presentation] MicroRNA-33 Deficiency Reduced Atherosclerosis Formation In Vivo (2012)
  • Author(s): Horie T, Baba O, Ono K, Kuwabara Y, Hasegawa K, Kume N, Yokode M, Kita T, and Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Los Angeles Convention CenterLos Angeles(U.S.A.)
• [Presentation] Symposium 6 (SY6) (HF) Diagnosis of Heart Failure Using Genetic Biomarker Increased MicroRNA-1 and MicroRNA-133a Levels in Serum of Patients with Cardiovascular Disease Indicate the Existence of Myocardial Damage (2012)
  • Author(s): Ono K
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] MicroRNA-33 regulates atherosclerosis formation (2012)
  • Author(s): Horie T, Baba O, Ono K, Watanabe S, Nishi H, Kinoshita M, Kuwabara Y, Chujo Y, Sowa N, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T.
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Circulating microRNA derived from damaged cardiomyocytes can regulate the gene expression in recipient cells. (2012)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Watanabe S, Kinoshita M, Baba O, Chujo Y, Kita T, Kimura T
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] MicroRNA 26b encoded by the intron of SCP1 has an antagonistic on its host gene and cardiac hypertrophy (2012)
  • Author(s): Sowa N, Ono K, Horie T, Hasegawa K, Kita T, Kimuta T
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] MicroRNA-33-deficiency reduces the progression of atherosclerotic plaque in apoE-/- mice (2012)
  • Author(s): Ono-K
  • Organizer: Cold spring harbor laboratory meeting. Regulatory and non-coding RNA.
  • Place of Presentation: Cold spring harbor laboratory, NY, USA
• [Presentation] MicroRNA regulation of lipid homeostasis. (2012)
  • Author(s): Ono-K
  • Organizer: 25th Spring Congress of Korean Diabetes Association
  • Place of Presentation: Hotel Inter-Burgo, Daegu, Korea
  • Invited
• [Presentation] MicroRNA 33 Deficiency Reduces Atherosclerotic Plaque progression in ApoE Knockout Mice. (2012)
  • Author(s): Baba-O
  • Organizer: European Society of Cardiology Congress 2012
  • Place of Presentation: Internationales Congress Center Munchen, Munich, Germany
• [Presentation] Interaction of S100A4 with p53 in fibroblasts modulates cardiac fibrosis through two distinct mechanisms. (2012)
  • Author(s): Tamaki-Y
  • Organizer: European Society of Cardiology Congress 2012
  • Place of Presentation: Internationales Congress Center Munchen, Munich, Germany
• [Presentation] MicroRNA 33 Deficiency in Leukocytes Reduced the Lipid Accumulation in Atherosclerotic Plaque in ApoE Knockout Mice. (2012)
  • Author(s): Baba-O
  • Organizer: American Heart Association Annual Scientific Sessions 2012
  • Place of Presentation: Los Angeles Convetion Center, LA, USA
• [Presentation] MicroRNA-33 Deficiency Reduced Atherosclerosis Formation In Vivo. (2012)
  • Author(s): Horie-T
  • Organizer: American Heart Association Annual Scientific Sessions 2012
  • Place of Presentation: Los Angeles Convetion Center, LA, USA
• [Presentation] Increased MicroRNA-1 and MicroRNA-133a Levels in Serum of Patients with Cardiovascular Disease Indicate the Existence of Myocardial Damage (2012)
  • Author(s): Ono K
  • Organizer: Japanese Circulation Society(招待講演)
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] MicroRNA-33 regulates atherosclerosis formation. (2012)
  • Author(s): Horie T, Baba O, Ono K, Watanabe S, Nishi H, Kinoshita M, Kuwabara Y, Chujo Y, Sowa N, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T.
  • Organizer: Japanese Circulation Society
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] Circulating microRNA derived from damaged cardiomyocytes can regulate the gene expression in recipient cells. (2012)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Watanabe S, Kinoshita M, Baba O, Chujo Y, Kita T, Kimura T.
  • Organizer: Japanese Circulation Society
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] MicroRNA 26b encoded by the intron of SCP1 has an antagonistic on its host gene and cardiac hypertrophy. (2012)
  • Author(s): Sowa N, Ono K, Horie T, Hasegawa K, Kita T, Kimuta T.
  • Organizer: Japanese Circulation Society
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] MicroRNA-33 Encoded by an Intron of Srebp2 Regulates HDL in vivo. (2011)
  • Author(s): Yeungnam University, Daegu(Korea) Koh Ono
  • Organizer: 2011AVDRC International Symposium, Intervention of Vascular Aging
  • Place of Presentation: College of Medicine, Yeungnam University, Daegu(Korea)
  • Year and Date: 2011-09-22
• [Presentation] MicroRNA 26b encoded by the introns of small CTD Phosphatases (SCPs) 1 has an antagonistic effect on its host gene and suppresses cardiac hypertrophy (2011)
  • Author(s): Sowa N, Ono K, Horie T, Hasegawa K, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Orland(U.S.A.)
• [Presentation] MicroRNA-1 and microRNA-133a elevations in serum of patients with cardiovascular disease indicate the existence of myocardial damage. (2011)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Watanabe S, Kinoshita M, Baba O, Chujo Y, Nagao K, Kojima Y, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Orlando(U.S.A.)
• [Presentation] Soluble vascular endothelial growth factor receptor-1 serves as a marker of cardiovascular risk in chronic kidney disease patients. (2011)
  • Author(s): Wada H, Ura S, Masunaga N, Akao M, Abe M, Funatsu J, Nakajima Y, Kanasaki M, Nakano T, Ono K, Morimoto T, Shimatsu A, Hasegawa K
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Orlando(U.S.A.)
• [Presentation] Plenary session. MicroRNA-33 Encoded by an Intron of Srebp2 Cooperates to Control HDL in Vivo (2011)
  • Author(s): Ono-K.
  • Organizer: 第75回日本循環器学会
  • Place of Presentation: 横浜市
• [Presentation] MicroRNA 26b encoded by the introns of small CTD Phosphatases (SCPs) 1 has an antagonistic effect on its host gene and suppresses cardiac hypertrophy. (2011)
  • Author(s): Sowa N, Ono K, Horie T, Hasegawa K, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions 2011
  • Place of Presentation: Orange County Convention Center(Orlando, Florida)
• [Presentation] MicroRNA-1 and microRNA-133a elevations in serum of patients with cardiovascular disease indicate the existence of myocardial damage. (2011)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Watanabe S, Kinoshita M, Baba O, Chujo Y, Nagao K, Kojima Y, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions 2011
  • Place of Presentation: Orange County Convention Center(Orlando, Florida)
• [Presentation] Soluble vascular endothelial growth factor receptor-1 serves as a marker of cardiovascular risk in chronic kidney disease patients. (2011)
  • Author(s): Wada H, Ura S, Masunaga N, Akao M, Abe M, Funatsu J, Nakajima Y, Kanasaki M, Nakano T, Ono K, Morimoto T, Shimatsu A, Hasegawa K
  • Organizer: American Heart Association Annual Scientific Sessions 2011
  • Place of Presentation: Orange County Convention Center(Orlando, Florida)
• [Presentation] MicroRNA-33 Encoded by an Intron of Srebp2 Regulates HDL in vivo. (2011)
  • Author(s): Ono K
  • Organizer: 2011AVDRC International Symposium, Intervention of Vascular Aging: New Frontiers(招待講演)
  • Place of Presentation: Yeungnam University(Daegu, Korea)
• [Presentation] MicroRNA-33 Encoded by an Intron of Srebp2 Cooperates to Control HDL in Vivo (2011)
  • Author(s): Ono K
  • Organizer: Japanese Circulation Society(招待講演)
  • Place of Presentation: パシフィコ横浜（横浜）
• [Book] 細胞工学 疾患エクソソーム (2013)
  • Author(s): 尾野 亘
  • Publisher: 秀潤社
• [Book] 細胞工学 疾患エクソソーム (2013)
  • Author(s): 尾野 亘
  • Publisher: 秀潤社
• [Book] Annual Review 糖尿病・代謝・内分泌 (2012)
  • Author(s): 尾野 亘
  • Publisher: 中外医学社
• [Book] Roles of MicroRNAs and Myocardial Cell Differentiation (2012)
  • Author(s): Tomohide Takaya
  • Publisher: Burlington: Academic Press
• [Book] Annual Review 糖尿病・代謝・内分泌2012 (2012)
  • Author(s): 尾野 亘
  • Publisher: 中外医学社
• [Book] Burlington: Academic Press (2012)
  • Author(s): Tomohide Takaya
  • Publisher: Roles of MicroRNAs and Myocardial Cell Differentiation.
• [Book] Annual Review 糖尿病・代謝・内分泌2012 (2011)
  • Author(s): 尾野 亘
  • Total Pages: 240
  • Publisher: 中外医学社
• [Book] Annual Review 糖尿病・代謝・内分泌2012 (2011)
  • Author(s): 尾野 亘
  • Total Pages: 240
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/metabolic/
• [Remarks] 京都大学循環器内科心血管疾患分子機構解明グループ
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/metabolic/
• [Patent(Industrial Property Rights)] 大動脈瘤および大血管の炎症抑制治療製材 (2012)
  • Inventor(s): 尾野 亘
  • Industrial Property Rights Holder: 尾野 亘
  • Filing Date: 2012-10-31
• [Patent(Industrial Property Rights)] 大動脈瘤および大血管の炎症抑制治療製剤 (2012)
  • Inventor(s): 尾野 亘
  • Industrial Property Rights Holder: 尾野 亘
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-10-31
  • Overseas