Identification of human DC and monocyte progenitors

• Project/Area Number: 15K15150
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: OHTEKI Toshiaki 東京医科歯科大学, 難治疾患研究所, 教授 (50233200)
• Co-Investigator(Renkei-kenkyūsha): ONAI Nobuyuki 東京医科歯科大学, 難治疾患研究所, 講師 (50323605)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ヒトcMop / 単球/マクロファージ / cGMP / rGMP / cMoP / GMP / プレ単球 / 単球 / マイクロアレイ / CDP / 樹状細胞 / マクロファージ

Outline of Final Research Achievements

Dendritic cells and monocytes/macrophages are critically involved in host defense and tissue pathology under steady-state and inflammatory conditions. A common monocyte progenitor (cMoP) that is strictly committed to the monocyte lineage has been recently identified in mice. In this study, we identified human cMoPs as a CLEC12AhiCD64hi subpopulation of conventional granulocyte-monocyte progenitors (cGMPs) in umbilical cord blood and in bone marrow. Human cMoPs gave rise to monocyte subsets without showing any potential for differentiating into myeloid or lymphoid cells. Within the cGMP population, we also identified revised GMPs that completely lacked DC and lymphoid potential. Our findings expand and revise the current understanding of human myeloid cell differentiation pathways.

Research Products

• [Journal Article] Identification of a human clonogenic progenitor with strict monocyte differentiation potential - a counterpart of mouse cMoPs. (2017)
  • Author(s): Kawamura S, Onai N, Miya F, Sato T, Tsunoda T, Kurabayashi K, Yotsumoto S, Kuroda S, Takenaka K, Akashi K and Ohteki T.
  • Journal Title: Immunity Volume: 46
  • Peer Reviewed
• [Journal Article] マクロファージの分化と多様性「免疫学のABC」 第２回） (2017)
  • Author(s): 樗木俊聡
  • Journal Title: 分子リウマチ治療2 Volume: 10 Pages: 46-49
• [Journal Article] Non-myeloablative preconditioning with ACK2 (anti-c-kit antibody) is efficient in bone marrow transplantation for murine models of mucopolysaccharidosis type II (2016)
  • Author(s): Yokoi, T., Yokoi, K., Akiyama, K., Higuchi, T., Shimada, Y., Kobayashi, H., Sato, T., Ohteki, T., Otsu, M., Nakauchi, H., Ida, H. and Ohashi, T
  • Journal Title: Mol Genet Meta Volume: 119 Issue: 3 Pages: 232-238
  • DOI: 10.1016/j.ymgme.2016.08.003
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Isolation of dendritic cell progenitor and bone marrow progenitor cells from mouse. (2016)
  • Author(s): Onai N, Ohteki T.
  • Journal Title: Methods Mol Biological Volume: 1423 Pages: 53-59
  • DOI: 10.1007/978-1-4939-3606-9_4
  • ISBN: 9781493936045, 9781493936069
  • Peer Reviewed
• [Journal Article] 樹状細胞前駆細胞および樹状細胞サブセットのソーティング (2016)
  • Author(s): 小内伸幸、樗木俊聡
  • Journal Title: 実験医学 最強のステップUPシリーズ 新版！フローサイトメトリー Volume: 別冊 Pages: 229-240
• [Journal Article] マクロファージ・樹状細胞の起源と多様性 (2016)
  • Author(s): 樗木俊聡
  • Journal Title: 医学のあゆみ マクロファージのすべて Volume: 259 Pages: 247-352
• [Journal Article] Cytosine-phosphorothionate- guanine oligodeoxynucleotides exacerbates hemophagocytosis by inducing tumor necrosis factor-α production in mice after bone marrow transplanation. (2016)
  • Author(s): Liu J, Guo YM, Onai N, Ohyagi H, Hirokawa M, Takahashi N, Tagawa H, Ubukawa K, Kobayahi I, Tezuka H, Minamiya Y, Ohteki T, and Sawada K.
  • Journal Title: Biol Blood Marrow Transplant 2015 Volume: 印刷中 Issue: 4 Pages: 627-636
  • DOI: 10.1016/j.bbmt.2015.12.018
  • Peer Reviewed / Open Access
• [Journal Article] Commensal Gram-positive bacteria initiates colitis by inducing monocyte/macrophage mobilization (2015)
  • Author(s): Yusuke Nakanishi, Taku Sato, and Toshiaki Ohteki.
  • Journal Title: Mucosal Immunology Volume: 8 Issue: 1 Pages: 152-160
  • DOI: 10.1038/mi.2014.53
  • Peer Reviewed / Open Access
• [Journal Article] Bacterial c-di-GMP affects hematopoietic stem/progenitors and their niches through STING. (2015)
  • Author(s): Kobayashi H, Kobayashi CI, Nakamura-Ishizu A, Karigane D, Haeno H, Yamamoto KN, Sato T, Ohteki T, Hayakawa Y, Barber GN, Kurokawa M, Suda T, and Takubo K.
  • Journal Title: Cell Reports Volume: 111 Issue: 1 Pages: 71-84
  • DOI: 10.1016/j.celrep.2015.02.066
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 免疫・細胞治療の基礎と応用 (2016)
  • Author(s): 樗木俊聡
  • Organizer: 相馬市歯科医師会地域学術講演会
  • Place of Presentation: 福島県相馬市 相馬フローラ
  • Year and Date: 2016-09-10
  • Invited
• [Presentation] Identification of mononuclear phagocyte progenitors. (2015)
  • Author(s): Ohteki T
  • Organizer: The 44th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: 北海道札幌市(札幌コンベンションセンター)
  • Year and Date: 2015-11-18
  • Int'l Joint Research / Invited
• [Presentation] 「免疫の司令塔、樹状細胞の源となる細胞の同定」 (2015)
  • Author(s): 樗木俊聡
  • Organizer: 第22回輸血細胞治療学会シンポジウム
  • Place of Presentation: 長野件北佐久郡(軽井沢プリンスホテル)
  • Year and Date: 2015-10-23
  • Invited
• [Presentation] Identity and flexibility of common dendritic cell progenitor. (2015)
  • Author(s): Ohteki T
  • Organizer: 4th Europian Congress of Immunology
  • Place of Presentation: ウィーン(オーストリア)
  • Year and Date: 2015-09-06
  • Int'l Joint Research
• [Book] Annual Review 血液（2015） (2015)
  • Author(s): 樗木俊聡
  • Total Pages: 285
  • Publisher: 中外医学社
• [Remarks] 東京医科歯科大学難治疾患研究所生体防御学分野
  • URL: http://www.tmd.ac.jp/mri/bre/index.html