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Generation of induced spermatogonial stem cells by direct reprogramming

Research Project

Project/Area Number 25660255
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Integrative animal science
Research InstitutionKitasato University

Principal Investigator

Kubota Hiroshi  北里大学, 獣医学部, 教授 (80263094)

Co-Investigator(Renkei-kenkyūsha) Kakiuchi Kazue  北里大学, 獣医学部, 助教 (90509184)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords幹細胞 / 分化・発生 / 生殖 / バイオテクノロジー / 精原幹細胞 / 初期化 / 人工幹細胞
Outline of Final Research Achievements

Ectopic expression of Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) in somatic cells has been shown to generate induced pluripotent stem cells (iPSCs), which are very similar to embryonic stem cells (ESCs), under ESC culture conditions. This study investigated whether somatic cells that were introduced Yamanaka factors can be reprogrammed into spermatogonial stem cells (SSCs) under SSC culture conditions. After introduction of expression plasmids for Yamanaka factors into male mouse embryonic fibroblasts (MEFs), they were cultured under ESC conditions or SSC conditions. Although iPSCs were generated in the ESC condition, neither SSC-like cells nor iPSCs were generated in SSC conditions. However, MEFs reprogrammed under the ESC condition followed by cultivation under the SSC condition generated undifferentiated cells with SSC characteristics, indicating the feasibility of generating induced SSCs.

Academic Significance and Societal Importance of the Research Achievements

精子の源となる精原幹細胞を人工多能性幹細胞(iPS細胞)のように体細胞から得ることができれば、優良個体や稀少動物種の繁殖に有用である。山中因子を導入して初期化した細胞を直接精原幹細胞の培養条件下で培養することにより精原幹細胞への分化誘導を試みたところ(ダイレクト・リプログラミング)、初期化の培養条件を検討することにより人工精原幹細胞の樹立の可能性が示唆された。本研究は新たな精子産生細胞の樹立に向けて重要な知見を示すものである。

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (7 results)

All 2014 2013 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] Cell-Surface DEAD-Box Polypeptide 4-Immunoreactive Cells and Gonocytes Are Two Distinct Populations in Postnatal Porcine Testes2014

    • Author(s)
      Kakiuchi K, Tsuda A, Goto Y, Shimada T, Taniguchi K, Takagishi K, Kubota H
    • Journal Title

      Biology of Reproduction

      Volume: 90 Issue: 4 Pages: 1-11

    • DOI

      10.1095/biolreprod.113.114405

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 精巣における細胞表面DDX4陽性細胞は生殖幹細胞か?2014

    • Author(s)
      米澤(垣内) 一恵, 久保田浩司
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      神奈川県 パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 哺乳動物精原幹細胞の共通性と多様性2014

    • Author(s)
      久保田浩司
    • Organizer
      京都大学霊長類研究所研究会 「霊長類への展開に向けた幹細胞・生殖細胞・エピゲノム研究」
    • Place of Presentation
      愛知県 京都大学霊長類研究所
    • Year and Date
      2014-08-26 – 2014-08-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Comparative nuclear proteomic analysis of stem spermatogonia and differentiating spermatogonia induced by retinoic acid2013

    • Author(s)
      Kakiuchi K, Takagishi K, Kubota H
    • Organizer
      12th Human Proteome Organization World Congress (HUPO 2013)
    • Place of Presentation
      神奈川県 パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Proteomic profiling of nuclear proteins in mouse spermatogonial stem cells undergoing differentiation2013

    • Author(s)
      Kakiuchi K, Takagishi K, Kubota H
    • Organizer
      第36回 日本分子生物学会
    • Place of Presentation
      兵庫県 神戸ポートアイランド
    • Related Report
      2013 Research-status Report
  • [Remarks] 北里大学獣医学部ホームページ

    • URL

      http://www.kitasato-u.ac.jp/vmas/faculty/as/news/n20140422.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] Global Medical Discovery Key Scientific Articles

    • URL

      https://globalmedicaldiscovery.com/key-scientific-articles/cell-surface-dead-box-polypeptide-4-immunoreactive-cells-gonocytes-two-distinct-populations-inpostnatal-porcine-testes/

    • Related Report
      2014 Annual Research Report

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Published: 2014-07-25   Modified: 2021-02-19  

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