Elucidation of human naive and primed induced pluripotent stem cells directly reprogrammed with measles virus vectors

• Project/Area Number: 16H06746
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Liao Jiyuan 東京大学, 医科学研究所, 特任研究員 (90781857)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: naive iPS細胞 / 麻疹ウイルスベクタ / 幹細胞 / Naive iPSCs / Measles virus / iPS細胞 / 麻疹ウイルスベクター / iPS細胞樹立法

Outline of Final Research Achievements

A novel non-integrating measles virus vectors (MVV) have been developed in our laboratory to safely generated iPSCs. Two kinds of different iPS colonies, which are naive-like iPSCs with dome shape morphology and conventional primed-like iPSCs with flat shape morphology, were directly generated via somatic cell reprogramming using our MVV system. In this study, we performed comparative analysis for molecular mechanisms including DNA methylation analysis in the conversion processes between the two types of iPSCs. The results showed that naive-iPSCs represented increased expression of early epiblast stem cell-related factors. Furthermore, the naive-like iPSCs showed low level of CpG methylation compared with primed-like iPSCs.　In this study, we revealed regulation mechanisms of gene expression in conversion of the two types of iPSCs, and these findings were considered to be very important for the development of regenerative medicine.

Research Products

• [Journal Article] Regulation of expression and trafficking of perforin-2 by LPS and TNF-α. (2017)
  • Author(s): Xiong P, Shiratsuchi M, Matsushima T, Liao J, Tanaka E, Nakashima Y, Takayanagi R, Ogawa Y
  • Journal Title: Cell Immunol Volume: 320 Pages: 1-10
  • DOI: 10.1016/j.cellimm.2017.07.001
  • Peer Reviewed
• [Presentation] Successful Reprogramming of Human Hematopoietic Subsets with Non-integrating RNA Measles Virus Vectors (2017)
  • Author(s): Jiyuan Liao, Hiroshi Kohara, Takafumi Hiramoto, Maino Tahara, Yoshie Ogawa, Nobuaki Karasawa, Chika Sakamoto, Makoto Takeda, Kenzaburo Tani
  • Organizer: 第8回JSH国際シンポジウム（宮崎）
  • Int'l Joint Research
• [Presentation] The utility of a recombinant measles virus in reprogramming with multiple human hematopoietic cells (2017)
  • Author(s): Liao Jiyuan, Hiroshi Kohara, Takafumi Hiramoto, Maino Tahara, Yoshie Ogawa, Nobuaki Karasawa, Chika Sakamoto, Yuto Takashima, Shohei Miyamoto, Makoto Takeda, Kenzaburo TaniHiroshi Kohara, Yoshie Ogawa, Shohei Miyamoto, Hiromi Ogura, Taiju Utsugisawa, Hitoshi Kanno, Kenzaburo Tani
  • Organizer: 第23回日本遺伝子細胞治療学会学術集会
• [Presentation] Reprogramming e ciency of human hematopoietic subsets by measles virus vectors (2017)
  • Author(s): 廖 紀元、小原 洋志、平本 貴史、田原 舞、小川 由恵、唐澤 伸明、坂本 千香、滝嶌 佑人、宮本 将平、竹 田 誠、谷 憲三朗
  • Organizer: 第17回日本再生医療学会
• [Presentation] Evaluation of measles virus vectors for reprogramming target human hematopietic subsets (2017)
  • Author(s): Liao Jiyuan, Hiroshi Kohara, Takafumi Hiramoto, Maino Tahara, Yoshie Ogawa, Nobuaki Karasawa, Chika Sakamoto, Yuto Takishima, Shohei Miyamoto, Makoto Takeda, Kenzaburo Tani
  • Organizer: 第79回日本血液学会学術集会
• [Remarks] 複数遺伝子搭載型新規麻疹ウィルスベクターを用いた安全かつ効率的なヒトiPS細胞樹立技術の開発
  • URL: http://www.jst.go.jp/saisei-nw/stemcellproject/kobetsu/kadai02-01-02.html