The establishment of cell maturation induction method by the gene body-centered epigenomic monitoring.

• Project/Area Number: 15K14431
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: Keio University
• Principal Investigator: Oda Mayumi 慶應義塾大学, 医学部(信濃町), 助教 (80567511)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: DNAメチル化 / 酸化的脱メチル化過程 / gene body領域 / 転写伸長反応 / 細胞成熟 / 心筋細胞 / ゲノム / エピゲノム / H3K36トリメチル化 / Gene body領域 / ゲノムワイド / 細胞分化 / 幹細胞 / 転写伸長

Outline of Final Research Achievements

This research project aims to evaluate and induce cell maturation on the basis of the possibility that the epigenetic state of the gene body region may be involved in cell maturation in a mammalian genome whose background is global DNA methylation modification. Comparison of cardiomyocytes and hepatocytes prior to the establishment of the initial maturation induction method revealed that the gene body epigenetic domain characterized by DNA hypomethylation is evident in cardiomyocytes and less pronounced in other cell types. Analysis of DNA demethylation metabolic intermediates in this cardiomyocyte-specific epigenetic domain also showed that the oxidative demethylation process might be involved in the construction of this active epigenetic domains.

Research Products

• [Int'l Joint Research] National Institute of Health(米国)
• [Int'l Joint Research] University of Toronto/Hospital for Sick Children/Ottawa Hospital Research Institute(Canada)
• [Journal Article] Violet Light Exposure Can Be a Preventive Strategy Against Myopia Progression. (2017)
  • Author(s): Torii H, Kurihara T, Seko Y, Negishi K, Ohnuma K, Inaba T, Kawashima M, Jiang X, Kondo S, Miyauchi M, Miwa Y, Katada Y, Mori K, Kato K, Tsubota K, Goto H, Oda M, Hatori M, Tsubota K.
  • Journal Title: EBioMedicine Volume: 15 Pages: 210-219
  • DOI: 10.1016/j.ebiom.2016.12.007
  • Peer Reviewed / Open Access
• [Journal Article] Expression analysis of the endogenous Zscan4 locus and its coding proteins in mouse ES cells and preimplantation embryos (2017)
  • Author(s): Ishiguro K., Nakatake Y., Chikazawa-Nohtomi N., Kimura H., Akiyama T., Oda M., Ko SBH., Ko MSH.
  • Journal Title: In Vitro Cell.Dev.Biol.-Anim. Volume: 53 Issue: 2 Pages: 179-190
  • DOI: 10.1007/s11626-016-0097-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epigenetic manipulation facilitates the generation of skeletal muscle cells from pluripotent stem cells. (2017)
  • Author(s): Tomohiko Akiyama, Shunichi Wakabayashi, Atsumi Soma, Saeko Sato, Yuhki Nakatake, Mayumi Oda, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B. H. Ko, Minoru S. H. Ko
  • Journal Title: Stem Cell International. Volume: 2017 Pages: 7215010-7215010
  • DOI: 10.1155/2017/7215010
  • Peer Reviewed / Open Access
• [Journal Article] Salt suppresses IFNγ inducible chemokines through the IFNγ-JAK1-STAT1 signaling pathway in proximal tubular cells. (2017)
  • Author(s): Arai Y, Takahashi D, Asano K, Tanaka M, Oda M, Ko SBH, Ko MSH, Mandai S, Nomura N, Rai T, Uchida S, Sohara E.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 46580-46580
  • DOI: 10.1038/srep46580
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells. (2016)
  • Author(s): Tomohiko Akiyama, Shunichi Wakabayashi, Atsumi Soma, Saeko Sato, Yuhki Nakatake, Mayumi Oda, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B. H. Ko, Minoru S. H. Ko.
  • Journal Title: Development Volume: 143 Issue: 20 Pages: 3674-3685
  • DOI: 10.1242/dev.139360
  • Peer Reviewed
• [Journal Article] H1foo Has a Pivotal Role in Qualifying Induced Pluripotent Stem Cells (2016)
  • Author(s): Kunitomi A, Yuasa S, Sugiyama F, Saito Y, Seki T, Kusumoto D, Kashimura S, Takei M, Tohyama S, Hashimoto H, Egashira T, Tanimoto Y, Mizuno S, Tanaka S, Okuno H, Yamazawa K, Watanabe H, Oda M, Kaneda R, Matsuzaki Y, Nagai T, Okano H, Yagami K, Tanaka M, Fukuda K.
  • Journal Title: Stem Cell Reports Volume: 6 Issue: 6 Pages: 825-833
  • DOI: 10.1016/j.stemcr.2016.04.015
  • NAID: 120007135348
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] H1foo has a pivotal role in qualifying induced pluripotent stem cells (2016)
  • Author(s): Akira Kunitomi, Shinsuke Yuasa, Fumihiro Sugiyama, Yuki Saito, T Seki, D Kusumoto, S Kashimura, M Takei, S Tohyama, H Hashimoto, T Egashira, Yoko Tanimoto, Saori Mizuno, S Tanaka, H Okuno, K Yamazawa, H Watanabe, M Oda, R Kaneda, Y Matsuzaki, H Okano, Ken-ichi Yagami, M Tanaka, K Fukuda
  • Journal Title: Stem Cell Research Volume: 印刷中
  • NAID: 120007135348
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells. (2015)
  • Author(s): Akiyama T, Xin L, Oda M, Sharov AA, Amano M, Piao Y, Cadet JS, Dudekula DB, Qian Y, Wang W, Ko SB, Ko MS
  • Journal Title: DNA research (Oxford Journals) Volume: 22 Issue: 5 Pages: 307-318
  • DOI: 10.1093/dnares/dsv013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Gene-body epigenetic domains participate in the coordination of gene-length heterogeneity in cardiomyocyte-specific gene transcription. (2017)
  • Author(s): Mayumi Oda, Shunichi Wakabayashi, N. Ari Wijetunga, Shinsuke Yuasa, Hirokazu Enomoto, Ruri Kaneda, Sung Han Yoon, Nishant Mittal, Qiang Jing, Masako Suzuki, John M. Greally, Keiichi Fukuda and Shinji Makino.
  • Organizer: Keystone Symposia: Heart development
  • Place of Presentation: Keysone, CO, USA
  • Year and Date: 2017-03-26
  • Int'l Joint Research
• [Presentation] 成熟細胞特有のgene body領域エピジェネティック・ドメインの構築とゲノム構成要素. (2016)
  • Author(s): 小田真由美, 福田恵一, 牧野伸司.
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜 (神奈川県)
  • Year and Date: 2016-11-30
• [Presentation] 多細胞生物のゲノムとエピゲノムの対話を垣間見る (2016)
  • Author(s): 小田真由美.
  • Organizer: 第4回 テニュアトラック教員による創発型シンポジウム ~革新~
  • Place of Presentation: 東京医科歯科大学 (東京都)
• [Presentation] Gene body epigenetic domains and gene-length play a role for cell type-specific gene expression (2016)
  • Author(s): Mayumi Oda
  • Organizer: Mini Seminar on Epigenetic regulation in mammalian cells.
  • Place of Presentation: 理研統合生命医科学センター (神奈川県)
• [Presentation] 心筋細胞成熟過程におけるgene body領域の5hmC維持と細胞種特異的エピゲノムの形成 (2015)
  • Author(s): 小田真由美、福田恵一、牧野伸司
  • Organizer: 分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 細胞種特異的遺伝子のgene bodyエピジェネティック修飾と遺伝子長 (2015)
  • Author(s): 小田真由美、福田恵一、牧野伸司
  • Organizer: 第２７回 高遠分子生物学シンポジウム
  • Place of Presentation: 延暦寺会館（滋賀県・大津市）
  • Year and Date: 2015-08-26
• [Presentation] 細胞種特異的遺伝子のgene body領域におけるDNA修飾の転写への影響 (2015)
  • Author(s): 小田真由美、福田恵一、牧野伸司
  • Organizer: NGS現場の会第４回研究会
  • Place of Presentation: つくば国際会議場（茨城県・つくば市）
  • Year and Date: 2015-07-01
• [Presentation] 選択と集中による細胞成熟過程のエピゲノム形成と細胞種特異的5hmC分布 (2015)
  • Author(s): 小田真由美、福田恵一、牧野伸司
  • Organizer: 第９回日本エピジェネティクス研究会年会
  • Place of Presentation: 学術総合センター一橋講堂（東京都・千代田区）
  • Year and Date: 2015-05-25
• [Remarks] 坂口講座テニュアトラックプログラム
  • URL: http://www.careerpath-prj.keio.ac.jp/sakaguchi/scholar/m_oda/
• [Remarks] Research Map
  • URL: https://researchmap.jp/odamame/
• [Remarks] 坂口講座テニュアトラックプログラム・小田真由美
  • URL: http://www.careerpath-prj.keio.ac.jp/sakaguchi/scholar/m_oda/
• [Remarks] Publication list
  • URL: https://scholar.google.com/citations?user=JI_XiDQAAAAJ&hl=en
• [Patent(Industrial Property Rights)] 体細胞から肺胞上皮細胞への分化用試薬及びその使用 (2017)
  • Inventor(s): 石井誠、（他7名）小田真由美
  • Industrial Property Rights Holder: 石井誠、（他7名）小田真由美
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-083814
  • Filing Date: 2017-04-20