Tetraploid embryonic stem cells maintain pluripotency and differentiation potency into three germ layers

• Project/Area Number: 25660254
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Integrative animal science
• Research Institution: Yamaguchi University
• Principal Investigator: KANO Kiyoshi 山口大学, 獣医学部, 准教授 (40312516)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 4倍体 / ES細胞 / マウス / 多倍体 / 多能性 / 胚性幹細胞 / 胚様体 / テラトーマ / 哺乳類 / ゲノム量

Outline of Final Research Achievements

Polyploid amphibians and fishes occur naturally in nature, while polyploid mammals do not. Thus, polyploidization is thought to be harmful during early mammalian development. However, the mechanisms through which polyploidization disrupts development are still poorly understood. In this study, we aimed to elucidate how genome duplication affects early mammalian development. We demonstrated that TESCs possessed essential pluripotency and differentiation potency to form teratomas, which differentiated into the three germ layers, including diploid embryonic stem cells. TESCs also exhibited sufficient expression and localization of pluripotent markers and retained the normal epigenetic status of relevant reprogramming factors. Thus, our findings suggested that mouse ESCs maintained intrinsic pluripotency and differentiation potential despite tetraploidization, providing insights into our understanding of developmental elimination in polyploid mammals.

Research Products

• [Presentation] マウス四倍体胚性幹細胞における倍数性変動の影響 (2014)
  • Author(s): 今井啓之、加納 聖、藤井 渉、高澤 建、脇谷晶一、西野光一郎、日下部健、木曾康郎
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] マウス４倍体胚性幹細胞の樹立と解析 (2014)
  • Author(s): 今井啓之、加納 聖、藤井 渉、日下部健、木曾康郎
  • Organizer: 第107回日本繁殖生物学会
  • Place of Presentation: 帯広畜産大学（北海道帯広市）
  • Year and Date: 2014-08-21 – 2014-08-23
• [Presentation] Analysis of tetraploid embryonic stem cells in mice. (2014)
  • Author(s): Imai H, Kano K, Fujii W, Kusakabe K, Kiso Y.
  • Organizer: The 12th stem cell research symposium
  • Place of Presentation: 九州大学医学部キャンパス（福岡県福岡市）
  • Year and Date: 2014-05-30 – 2014-05-31
• [Presentation] Analysis of tetraploid embryonic stem cells in mice (2013)
  • Author(s): Imai H, Fujii W, Kusakabe K, Kiso Y, Kano K.
  • Organizer: 26th annual Mouse Molecular Genetics meeting
  • Place of Presentation: Cambridge（United Kingdom）
• [Presentation] マウス４倍体胚性幹細胞の樹立とその特性に関する研究 (2013)
  • Author(s): 今井啓之、加納 聖、 藤井 渉、日下部 健、木曾 康郎
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場（神戸市）
• [Book] DDR mouse models (2015)
  • Author(s): Kiyoshi Kano, Ken Takeshi Kusakabe, Yasuo Kiso
  • Total Pages: 35
  • Publisher: Springer
• [Remarks] 山口大学共同獣医学部発生学分野
  • URL: http://ds0.cc.yamaguchi-u.ac.jp/~kanokiyo/index.html