The role of nuclear structure and an epigenetic switch in spermatogonial stem cell differentiation

• Project/Area Number: 26860137
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Yokohama City University
• Principal Investigator: TOMIZAWA Shinichi 横浜市立大学, 医学部, 助教 (00704628)
• Research Collaborator: ITOH Takashi 九州大学, 大学院医学研究院, 教授 (90201326)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 生殖細胞 / エピジェネティクス / ヒストン修飾 / 幹細胞 / 遺伝子 / ヒストン / 分化 / 精子形成

Outline of Final Research Achievements

It is well established that long-term spermatogenesis in mammals is supported by spermatogonial stem cells (SSCs). However, the molecular mechanisms governing SSC maintenance and differentiation is poorly understood. This study focused on dynamic changes in nuclear structure and epigenetic status that occur during SSC differentiation. These changes are important for gene expression programs and hence may greatly contribute to the conversion of cellular characteristics as SSCs differentiate. To identify the epigenetic changes in more detail, SSCs and progenitor cells were sorted and the global epigenetic status of each cell population was analyzed.

Research Products

• [Journal Article] DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal mouse testis. (2015)
  • Author(s): Kubo N, Toh H, Shirane K, Shirakawa T, Kobayashi H, Sato T, Sone H, Sato Y, Tomizawa S, Tsurusaki Y, Shibata H, Saitsu H, Suzuki Y, Matsumoto N, Suyama M, Kono T, Ohbo K, Sasaki H.
  • Journal Title: BMC Genomics. Volume: 16 Issue: 1 Pages: 624-624
  • DOI: 10.1186/s12864-015-1833-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epigenetic regulation in stem cell development, cell fate conversion, and reprogramming. (2015)
  • Author(s): Kazuyuki Ohbo, Shin-ichi Tomizawa
  • Journal Title: Biomolecular Concepts Volume: 6 Issue: 1 Pages: 1-9
  • DOI: 10.1515/bmc-2014-0036
  • Peer Reviewed
• [Presentation] Kmt2b regulates spermatogonial stem cell differentiation and marks primed genes for developmental potential. (2016)
  • Author(s): Tomizawa S, Kobayashi Y, Shirakawa T, Peters AHFM, Anastassiadis K, Stewart AF, Ohbo K
  • Organizer: EMBO Conference: From Functional Genomics to Systems Biology
  • Place of Presentation: Heidelberg (ドイツ)
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Role of histone methyltransferase Mll2 for adult testicular germ cell differentiation. (2016)
  • Author(s): Tomizawa S, Kobayashi Y, Shirakawa T, Dahl A, Alexopoulou D, Anastassiadis K, Stewart AF, Ohbo K
  • Organizer: Gordon Research Conference, Chromatin Structure & Function
  • Place of Presentation: Les Diablerets (スイス)
  • Year and Date: 2016-05-22
  • Int'l Joint Research
• [Presentation] Role of histone methyltransferase Mll2 for male germ cell development (2015)
  • Author(s): Shin-ichi Tomizawa, Takayuki Shirakawa, Konstantinos Anastassiadis, A. Francis Stewart, Kazuyuki Ohbo
  • Organizer: Keyston Symposia, Transcriptional and Epigenetic Influences on Stem Cell States
  • Place of Presentation: Colorado, USA
  • Year and Date: 2015-03-23 – 2015-03-28
• [Remarks] 横浜市立大学医学部組織学
  • URL: http://www-user.yokohama-cu.ac.jp/~finemorp/
• [Remarks] 横浜市立大学 医学部 組織学
  • URL: http://www-user.yokohama-cu.ac.jp/~finemorp/