High-Efficiency Differentiation of Auditory Neurons from Bone Marrow Mesenchymal Stem Cells Aiming at Regenerative Therapy of Auditory Nerve.

• Project/Area Number: 24592567
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Health Sciences University of Hokkaido (2014-2015); Fujita Health University (2012-2013)
• Principal Investigator: Shimomura Atsushi 北海道医療大学, リハビリテーション科学部, 教授 (50340237)
• Co-Investigator(Kenkyū-buntansha): KOGO AKIKO 群馬大学, 大学院医学系研究科, 講師 (20340242) ; NOMURA RYUJI 藤田保健衛生大学, 医学部, 講師 (20325161)
• Co-Investigator(Renkei-kenkyūsha): TAKUMI YUTAKA 信州大学, 学術研究院医学系, 准教授 (70312501)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 骨髄由来間葉系幹細胞 / グルタミン酸作動性ニューロン / 感音難聴 / 聴神経 / 再生治療 / エピジェネティック / グルタミン作動性ニューロン / エピジェネティックス / 感音性難聴

Outline of Final Research Achievements

The aim of our study is to develop the technique for high-efficiency differentiation of auditory neurons from bone marrow mesenchymal stem cells (BMSC). The transcription factor Tlx3 and Pax2 is essential for auditory neural development. Here, we found that Tlx3 and Pax2 regulate auditory neural differentiation through their interaction with epigenetic enzymes. Our results suggest that reagents that can affect the activity of these enzymes might be useful for high-efficiency differentiation of auditory neurons from BMSC.

Research Products

• [Int'l Joint Research] インディアナ大学(米国)
• [Journal Article] Tlx3 Promotes Glutamatergic Neuronal Subtype Specification through Direct Interactions with the Chromatin Modifier CBP. (2015)
  • Author(s): Atsushi Shimomura, Dharmeshkumar Patel, Sarah M. Wilson, Karl R. Koehler, Rajesh Khanna, and Eri Hashino.
  • Journal Title: Plos One Volume: 10 Issue: 8 Pages: e0135060-e0135060
  • DOI: 10.1371/journal.pone.0135060
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Requirement of DLG1 for cardiovascular development and tissue elongation 1 during cochlear, enteric, and skeletal development: possible role in convergent extension. (2015)
  • Author(s): Akiko Iizuka-Kogo, Takao Senda, Tetsu Akiyama, Atsushi Shimomura, Ryuji Nomura, Yoshimi Hasegawa, Ken-ichi Yamamura, Hiroshi Kogo, Nobuhiko Sawai, Toshiyuki Matsuzaki
  • Journal Title: PLoS ONE Volume: 10 Issue: 4 Pages: e0123965-e0123965
  • DOI: 10.1371/journal.pone.0123965
  • Peer Reviewed / Open Access
• [Journal Article] Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia (2014)
  • Author(s): Takanori Onouchi, Katsunori Kobayashi, Kazuyoshi Sakai, Atsushi Shimomura, Ron Smits, Chiho Sumi-Ichinose, Masafumi Kurosumi Keizo Takao, Ryuji Nomura, Akiko Iizuka-Kogo, Hidenori Suzuki,Kazunao Kondo, Tetsu Akiyama Tsuyoshi Miyakawa Riccardo Fodde and Takao Senda, Riccardo Fodde, Takao
  • Journal Title: Molecular Brain Volume: 7 Issue: 1 Pages: 21-21
  • DOI: 10.1186/1756-6606-7-21
  • Peer Reviewed / Open Access
• [Journal Article] Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1 (2013)
  • Author(s): Shimomura A, Takasaki A, Nomura R, Hayashi N, Senda T
  • Journal Title: Medical Molecular Morphology Volume: 46 Issue: 1 Pages: 14-19
  • DOI: 10.1007/s00795-012-0002-z
  • NAID: 10031171359
  • Peer Reviewed
• [Presentation] Tlx3 promote glutamatergic neuronal differentiation through the interaction with epigenetic co-factor CBP. (2015)
  • Author(s): Atsushi Shimomura、Dharmeshkumar Patel、Sarah M. Wilson、Karl R. Koehler、Rajesh Khanna、Eri Hashino
  • Organizer: 第120回日本解剖学会学術集会
  • Place of Presentation: 兵庫県神戸市 神戸国際会議場・展示場
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Tlx3はエピジェネティック因子CBPとの相互作用によりグルタミン酸作動性ニューロンへの分化を運命づける (2014)
  • Author(s): 下村 敦司、Dharmeshkumar Patel、Sarah M. Wilson、Karl R. Koehler、Rajesh Khanna、Eri Hashino
  • Organizer: 第60回日本解剖学会東北・北海道連合支部学術集会
  • Place of Presentation: 福島県福島市 福島学院大学 福島駅前キャンパス
  • Year and Date: 2014-09-06 – 2014-09-07
• [Presentation] Essential role for CBP in Tlx3-mediated neuronal differentiation from embryonic stem cells. (2013)
  • Author(s): Atsushi Shimomura, Patel D. Wilson, Rajesh Khanna and Eri Hashino
  • Organizer: 36th annual Meeting of the Association for Research in Otolaryngology.
  • Place of Presentation: Baltimore, USA
• [Book] Trends in Cell Signaling Pathways in Neuronal Fate Decision. (2013)
  • Author(s): Atsushi Shimomura and Eri Hashino
  • Total Pages: 21
  • Publisher: INTECH