Tracking of microglial development and differentiation in the developing brain

• Project/Area Number: 26461556
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: SAKUMA Hiroshi 公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, プロジェクトリーダー (50425683)
• Research Collaborator: IGARASHI Ayuko ; SAIKA Reiko ; SUZUKI Tomonori ; SHIMA Taiki
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ミクログリア / アストロサイト / インターロイキン34 / P2Y12受容体 / NLRP3 インフラマソーム / ADP / NF-κB / NLRP3インフラマソーム / 骨髄未分化細胞 / IL-34 / TGFβ / Time-lapse imaging / 造血幹細胞 / 前駆細胞

Outline of Final Research Achievements

Development and differentiation of microglia in the developing brain were studied using in vitro co-culture model. After microglial depletion using CD11b-conjugated microbes, the number of microglia rapidly increased. When bone marrow lineage-negative cells were co-cultured with astrocytes, they differentiated into microglia-like cells with assists of IL-34 and TGFβ. Microglial P2Y12 purinergic receptor played pivotal role in the activation of NLRP inflammasome.

Research Products

• [Journal Article] Cytokine-induced differentiation of hematopoietic cells into microglia-like cells in?vitro (2018)
  • Author(s): Igarashi Ayuko、Sakuma Hiroshi、Hayashi Masaharu、Noto Daisuke、Miyake Sachiko、Okumura Akihisa、Shimizu Toshiaki
  • Journal Title: Clinical and Experimental Neuroimmunology Volume: 8 Issue: 2 Pages: 139-149
  • DOI: 10.1111/cen3.12429
  • Peer Reviewed / Open Access
• [Journal Article] Effects of antiepileptic drugs on microglial properties (2018)
  • Author(s): Taiki Shima, Hiroshi Sakuma, Tomonori Suzuki, Kuniko Kohyama, Takako Matsuoka, Masaharu Hayashi, Akihisa Okumura, Toshiaki Shimizu
  • Journal Title: Epilepsy & Seizure Volume: 10 Issue: 1 Pages: 22-32
  • DOI: 10.3805/eands.10.22
  • NAID: 130006721857
  • ISSN: 1882-5567
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-101a regulates microglial morphology and inflammation (2017)
  • Author(s): Saika Reiko、Sakuma Hiroshi、Noto Daisuke、Yamaguchi Shuhei、Yamamura Takashi、Miyake Sachiko
  • Journal Title: J Neuroinflammation Volume: 14(1) Issue: 1 Pages: 109-109
  • DOI: 10.1186/s12974-017-0884-8
  • Peer Reviewed / Open Access
• [Journal Article] Development of a culture system to induce microglia-like cells from hematopoietic cells. (2014)
  • Author(s): Noto D, Sakuma H, Takahashi K, Yamada M, Yamamura T, Miyake S
  • Journal Title: Neuropathol Appl Neurobiol Volume: in press Issue: 6 Pages: 697-713
  • DOI: 10.1111/nan.12086
  • Peer Reviewed / Open Access
• [Presentation] 骨髄未分化細胞からミクログリア様細胞への分化に対するコロニー刺激因子の影響 (2016)
  • Author(s): 五十嵐鮎子、佐久間啓、神山邦子、鈴木智典、嶋泰樹、林雅晴
  • Organizer: 第28回日本神経免疫学会学術集会
  • Place of Presentation: 長崎ブリックホール（長崎県長崎市）
  • Year and Date: 2016-09-29
• [Presentation] P2Y12受容体シグナルはミクログリアにおけるサイトカイン産生を促進する (2016)
  • Author(s): 鈴木智典、上野太郎、林雅晴、佐久間啓
  • Organizer: 第28回日本神経免疫学会学術集会
  • Place of Presentation: 長崎ブリックホール（長崎県長崎市）
  • Year and Date: 2016-09-29
• [Presentation] CRISP/Cas9 systemを用いたknockout/downミクログリア細胞株の樹立 (2016)
  • Author(s): 鈴木智典、上野太郎、林雅晴、佐久間啓
  • Organizer: 第58回日本小児神経学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-06-03
• [Presentation] CD11b陽性細胞を除去した混合グリア培養におけるミクログリアの再増殖 (2015)
  • Author(s): 佐久間 啓，鈴木 智典，五十嵐 鮎子，神山 邦子，林 雅晴，三宅 幸子
  • Organizer: 第27回日本神経免疫学会学術集会
  • Place of Presentation: 長良川国際会議場（岐阜県、岐阜市）
  • Year and Date: 2015-09-15
• [Presentation] Interleukin-34 facilitates commitment of hematopoietic cells to micloglia-like cells (2015)
  • Author(s): Hiroshi Sakuma, Tomonori Suzuki, Masaharu Hayashi, Daisuke Noto, Reiko Saika, Takashi Yamamura, Sachiko Miyake
  • Organizer: 第57回日本小児神経学会学術集会
  • Place of Presentation: 帝国ホテル大阪（大阪府、大阪市）
  • Year and Date: 2015-05-28