Regulation of lineage fate in hematopoietic stem cells by Bach2(Fostering Joint International Research)

• Project/Area Number: 15KK0328
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: Ari Itoh-Nakadai 東北大学, 加齢医学研究所, 助教 (90749772)
• Research Collaborator: McHeyzer-Williams Michael スクリプス研究所, Immunology and Microbiology, 教授
• Project Period (FY): 2015 – 2017
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
• Keywords: 免疫記憶 / 獲得免疫 / 抗体産生 / 形質細胞 / メタロチオネイン / 亜鉛 / 長期生存細胞 / １細胞RNA-Seq / 細胞長期生存 / 単一細胞遺伝子解析 / RNA-Seq / 長寿命 / 免疫学 / 単一細胞解析

Outline of Final Research Achievements

Long-living plasma cells in bone marrow are key player of the memory of immunity. To elucidate the mechanism of long-living on plasma cells, we performed gene expression analysis using single cell RNA-sequencing (scRNA-seq). scRNA-seq analysis showed that MT1 and MT2 had high expression in bone marrow. These gene showed high correlation as expression level. We found that Hmox1 (HO-1) and Herped1, which are genes of anti-stress factors, highly expressing in MTs expressing cells in bone marrow. IL-6 stimulation increased MT1 and MT2 gene expression in spleen plasma cells. These result suggested that MT expressing cells have recieved survival factor stimulation in bone marrow.

Research Products

• [Int'l Joint Research] スクリプス研究所(米国) (2016)
  • Year and Date: 2016-05-29
• [Journal Article] Bone marrow PDGFRa+Sca-1+ enriched mesenchymal stem cells support survival of and antibody production by plasma cells in vitro through IL-6. (2018)
  • Author(s): Atsuko Kayaba, Ari Itoh-Nakadai, Kunimichi Niibe, Matsuyuki Shirota, Ryo Funayama, Akiko Sugahara-Tobinai, Yi Li Wong, Masanori Inui, Keiko Nakayama, and Toshiyuki Takai.
  • Journal Title: Int Immu Volume: in press Issue: 6 Pages: 241-253
  • DOI: 10.1093/intimm/dxy018
  • Peer Reviewed / Open Access
• [Journal Article] A Bach2-Cebp gene regulatory network for the commitment of multipotent hematopoietic progenitors. (2017)
  • Author(s): Itoh-Nakadai, A., Matsumoto, M., Kato, H., Sasaki, J., Uehara, Y., Sato, Y., Ebina-Shibuya, R., Morooka, M., Funayama, R., Nakayama, K., Ochiai, K., Muto, A. and Igarashi, K.
  • Journal Title: Cell Reports Volume: 18 Issue: 10 Pages: 2401-2414
  • DOI: 10.1016/j.celrep.2017.02.029
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Secretory leukocyte peptidase inhibitor (SLPI) is highly expressed in long-lived plasma cells (2017)
  • Author(s): Ari Itoh-Nakadai, Toshiyuki Takai
  • Organizer: Keystone Symposia: B Cells and T Follicular Helper Cells -Controlling Long-Lived Immunity (D2)
  • Place of Presentation: British Columbia, Canada
  • Year and Date: 2017-04-23
  • Int'l Joint Research
• [Presentation] Secretory leukocyte peptidase inhibitor (SLPI) is highly expressed in long-lived plasma cells (2017)
  • Author(s): Ari Itoh-Nakadai, Toshiyuki Takai
  • Organizer: The Inaugural Chiba University - UC San Diego Symposium on Mucosal Immunology, Allergy and Vaccines: Impact on Mucosal Diseases and Global Health
  • Place of Presentation: San Diego, USA
  • Year and Date: 2017-02-21
  • Int'l Joint Research
• [Presentation] Secretory leukocyte peptidase inhibitor (SLPI) is highly expressed in long-lived plasma cells (2017)
  • Author(s): Itoh-Nakadai A, Kayaba A and Takai T
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] Secretory leukocyte peptidase inhibitor (SLPI) is highly expressed in long-lived plasma cells (2017)
  • Author(s): Itoh-Nakadai A, Kayaba A and Takai T
  • Organizer: 5th Annual meeting of the international cytokine & interferon society
  • Int'l Joint Research
• [Presentation] Secretory leukocyte peptidase inhibitor (SLPI) is highly expressed in long-lived plasma cells (2017)
  • Author(s): Itoh-Nakadai A, Kayaba A and Takai T
  • Organizer: Keystone symposia
  • Int'l Joint Research
• [Presentation] 長寿命形質細胞の免疫記憶維持の解明 (2017)
  • Author(s): 伊藤亜里、萱場敦子、高井俊行
  • Organizer: 第3回日本骨免疫学会