The histone demethylase KDM2A regulates differentiation of spermatogonia in mice.

• Project/Area Number: 15K18386
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: The University of Tokyo
• Principal Investigator: Ozawa Manabu 東京大学, 医科学研究所, 准教授 (80608787)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 精原細胞 / 精原幹細胞 / 精巣 / ヒストン / 精子形成 / エピジェネティクス

Outline of Final Research Achievements

Modifications of histone residue, known as epigenetics, play important roles for development or differentiation of various types of cells including germ cells. KDM2A, a protein catalyzing demethylation of H3K4 or H3K36, is highly expressed in testis, whereas its roles in spermatogenesis is poorly understood. In this project, we have developed germ cell specific Kdm2a conditional knockout mouse (Kdm2a-cKO) and determined functional roles of KDM2A on spermatogenesis. Germ cell-specific Kdm2a-cKO mouse are totally infertile, and showed drastic abnormality in spermatogenesis, e.g., few sperm could be recovered from epididymis. Further analysis have revealed that mTORC activity, and important signal transduction for inducing differentiation of spermatogonia, is significantly weaker in the Kdm2a-cKO spermatogonia. These results indicated Kdm2a regulates spermatogonial differentiation by modulating mTORC activity.

Research Products

• [Int'l Joint Research] University of Florida(米国)
• [Journal Article] WNT regulation of embryonic development likely involves pathways independent of nuclear CTNNB1 (2017)
  • Author(s): Tribulo Paula、Moss James I、Ozawa Manabu、Jiang Zongliang、Tian Xiuchun (Cindy)、Hansen Peter J
  • Journal Title: Reproduction Volume: 153 Issue: 4 Pages: 405-419
  • DOI: 10.1530/rep-16-0610
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of gene expression in the bovine blastocyst by colony stimulating factor 2 (2016)
  • Author(s): Ozawa M, Sakatani M, Dobbs K, Kannampuzha-Francis J, Hansen PJ.
  • Journal Title: BMC Research Notes Volume: 9 Issue: 1 Pages: 250-250
  • DOI: 10.1186/s13104-016-2038-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex. (2016)
  • Author(s): Zhang X, Chen H, Wu X, Kodani A, Fan J, Doan R, Ozawa M, Ma J, Yoshida N, Reiter JF, Black DL, Kharchenko PV, Sharp PA, Walsh CA.
  • Journal Title: Cell Volume: 166 Issue: 5 Pages: 1147-1162
  • DOI: 10.1016/j.cell.2016.07.025
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The requirement for protein kinase C delta (PRKCD) during preimplantation bovine embryo development. (2016)
  • Author(s): Yang QE, Ozawa M, Zhang K, Johnson S, Ealy AD.
  • Journal Title: Reproduction, Fertility and Development Volume: 28 Issue: 4 Pages: 482-490
  • DOI: 10.1071/rd14160
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The histone demethylase FBXL10 regulates the proliferation of spermatogonia and ensures long-term sustainable spermatogenesis in mice (2016)
  • Author(s): Ozawa M, Fukuda T, Nakamoto R, Honda H, Yoshida N
  • Journal Title: Biology of Reproduction Volume: 94 Issue: 4 Pages: 1-11
  • DOI: 10.1095/biolreprod.115.135988
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Polypyrimidine tract binding protein (Ptbp1) expression by Sertoli cells is essential for sperm production (2018)
  • Author(s): Ozawa M, Ikawa M, Yoshida N.
  • Organizer: Society for the Study of Reproduction
  • Int'l Joint Research
• [Presentation] The histone demethylase KDM2A regulates differentiation of spermatogonia in mice. (2017)
  • Author(s): Ozawa M, Kawakami E, Tokunaga A, Sakamoto R, Yoshida N.
  • Organizer: World Congress of Reproductive Biology
  • Int'l Joint Research
• [Presentation] The histone demethylase FBXL10 regulates the proliferation of spermatogonia and ensures long-term sustainable spermatogenesis in mice (2016)
  • Author(s): Ozawa M, Fukuda T, Sakamoto R, Honda H, Yoshida N
  • Organizer: Annual meeting of the Society for the Study of Reproduction
  • Place of Presentation: San Diego, CA USA
  • Year and Date: 2016-07-16
  • Int'l Joint Research
• [Presentation] The histone demethylase FBXL10 regulates the proliferation of spermatogonia and ensures long-term sustainable spermatogenesis in mice (2016)
  • Author(s): Ozawa M, Fukuda T, Sakamoto R, Honda H, Yoshida N
  • Organizer: 49th Annual Meeting of the Society for the Study of Reproduction
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2016-07-16
  • Int'l Joint Research
• [Presentation] ヒストン脱メチル化酵素Kdm2aは精原細胞の自己複製と分化のバランスを調整する (2015)
  • Author(s): 小沢学 川上絵里 徳永暁憲 坂本怜子 吉田進昭
  • Organizer: 第３８回 日本分子生物学会年会
  • 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] Histone demethylase Fbxl11 regulates balance between self-renew and differentiation of spermatogonia in mice (2015)
  • Author(s): Ozawa M, Kawakami E, Tokunaga A, Sakamoto R, Yoshida N
  • Organizer: 48th Annual Meeting of the Society for the Study of Reproduction
  • Place of Presentation: San Juan, Puerto Rico, USA
  • Year and Date: 2015-06-18
  • Int'l Joint Research