Testing possible contribution of maternal microchimeric cells to biliary atresia

• Project/Area Number: 17K19547
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pathology, Infection/Immunology, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: IRIE Naoki 東京大学, 大学院理学系研究科(理学部), 准教授 (10536121)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マイクロキメリズム / 発生生物学 / 母由来細胞 / エピジェネティクス / 母児間免疫病 / 発生 / 先天異常

Outline of Final Research Achievements

Previous studies clarified that mammals, including ourselves, have non-self, maternal cells circulating in our body, however, exact entities and roles of these cells remain elusive. By taking advantages of human diphtheria toxin receptor, together with IRES associated GFP expressing system, we have developed transgenic mice which can specifically remove maternal cells. We also found that frequency of maternal cells could differ largely by individual infants. Maternal cells are reported to associate with seemingly contradictory phenomena, such as regeneration, immune tolerance, and inflammatory disease, and we hope our findings would provide basis for resolving this problem.

Academic Significance and Societal Importance of the Research Achievements

私達の体内には、妊娠中に入り込んできた母親細胞がなぜか存在しており、一生涯こうしたキメラ状態が続きます。しかし、こうした母親細胞が実際に何をしているのか、どういった細胞群なのかについては謎が多く残っています。本研究ではまず、この母親細胞が存在しない条件をつくりだすための遺伝子組み換えマウスをつくりだし、また、検出が難しい母親細胞の数を数えるということに成功しました。今後、母親細胞がどういった役割を担っているのか、いったいどういった細胞達なのかを解明する手がかりになることが期待されます。

Research Products

• [Presentation] 胎仔に移入する母由来間イクロキメリズム細胞とは何者なのだろうか？ (2019)
  • Author(s): Kana Fujimoto, Naoki Irie
  • Organizer: The 42nd Annual Meeting of the Molecular Biology Society of Japan
• [Presentation] 胎児期に移入する母親細胞とはどのような細胞なのだろう？ (2019)
  • Author(s): Kana Fujimoto, Naoki Irie
  • Organizer: 第31回 高遠・分子細胞生物学シンポジウム
• [Presentation] Maternal microchimeric cells in shaping the developing immune system (2019)
  • Author(s): Flore Castellan, Naoki Irie
  • Organizer: EMBO Single Cell Biology workshop
  • Int'l Joint Research
• [Presentation] Maternal microchimeric cells in shaping the developing immune system (2019)
  • Author(s): Flore Castellan, Naoki Irie
  • Organizer: 52nd Annual Meeting of the Japanese Society of Developmental Biology
• [Presentation] Characterization of the phenotypes and functions of maternal cells in biliary atresia (2018)
  • Author(s): Flore Castellan, Naoki Irie
  • Organizer: EMBO Practical course “Molecular interrogation of single-cells to decipher population heterogeneity and plasticity”
  • Int'l Joint Research