Measuring shape and movement of hematopoietic stem cells

• Project/Area Number: 18K19570
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Takubo Keiyo 国立研究開発法人国立国際医療研究センター, その他部局等, 生体恒常性プロジェクト長 (50502788)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 造血幹細胞 / 造血前駆細胞 / 幹細胞性 / イメージング / 画像解析

Outline of Final Research Achievements

We established a two-dimensional platform for measuring “shape” and “movement” of hematopoietic stem cells. We next isolated steady-state hematopoietic stem cells and differentiated progenitor cells using a flow cytometer based on surface markers. Then, we collected data on "shape" and "moving" using the platform over time. In addition, by adding a fluorophore-labeled antibody to the culture, we analyze whether there is a change in "shape" and "movement" before and after the timing of differentiation. The obtained data were quantitatively analyzed using an image analysis program, and the characteristics specific to hematopoietic stem cells were obtained.

Academic Significance and Societal Importance of the Research Achievements

本研究より、表面マーカーに依存した細胞同定、という血液学研究の技術的ボトルネックの解消につながる成果が得られた。既存の手法とは全く違う方法からの細胞同定手法の萌芽が得られたといえ、造血分野にとどまらない創造的な外挿性・発展性のある技術への足掛かりになることが期待される。

Research Products

• [Int'l Joint Research] University of Cambridge(英国)
• [Int'l Joint Research] Karolinska Institutet(スウェーデン)
• [Journal Article] Discrimination of dormant and active hematopoietic stem cells by G0 markers reveals dormancy regulation by cytoplasmic calcium. (2019)
  • Author(s): 5.Fukushima T, Tanaka Y, Hamey FK, Chang CH, Oki T, Asada S, Hayashi Y, Fujino T, Yonezawa T, Takeda R, Kawabata KC, Fukuyama T, Umemoto T, Takubo K, Takizawa H, Goyama S, Ishihama Y, Honda H, Gottgens B, Kitamura T.
  • Journal Title: Cell Rep Volume: 29 Issue: 12 Pages: 4144-4158
  • DOI: 10.1016/j.celrep.2019.11.061
  • NAID: 120006892032
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Type I Interferon Delivery by iPSC-Derived Myeloid Cells Elicits Antitumor Immunity via XCR1+ Dendritic Cells. (2019)
  • Author(s): Tsuchiya N, Zhang R, Iwama T, Ueda N, Liu T, Tatsumi M, Sasaki Y, Shimoda R, Osako Y, Sawada Y, Kubo Y, Miyashita A, Fukushima S, Cheng Z, Nakaki R, Takubo K, Okada S, Kaneko S, Ihn H, Kaisho T, Nishimura Y, Senju S, Endo I, Nakatsura T, Uemura Y.
  • Journal Title: Cell Rep. Volume: 29 Issue: 1 Pages: 162-175
  • DOI: 10.1016/j.celrep.2019.08.086
  • Peer Reviewed / Open Access
• [Journal Article] Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses (2019)
  • Author(s): Nagai M、Noguchi R、Takahashi D、Morikawa T、Koshida K、Komiyama S、Ishihara N、Yamada T、Kawamura YI.、Muroi K、Hattori K、Kobayashi N、Fujimura Y、Hirota M、Matsumoto R、Aoki R、Tamura-Nakano M、Sugiyama M、Katakai T、Sato S、Takubo K、Dohi T、Hase K
  • Journal Title: Cell Volume: 178 Issue: 5 Pages: 1072-1087
  • DOI: 10.1016/j.cell.2019.07.047
  • Peer Reviewed
• [Journal Article] Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo. (2019)
  • Author(s): Kobayashi H, Morikawa T, Okinaga A, Hamano F, Hashidate-Yoshida T, Watanuki S, Hishikawa D, Shindou H, Arai F, Kabe Y, Suematsu M, Shimizu T, Takubo K.
  • Journal Title: Cell Reports Volume: 28 Issue: 1 Pages: 145-158
  • DOI: 10.1016/j.celrep.2019.06.008
  • Peer Reviewed / Open Access
• [Journal Article] ATP turnover and glucose dependency in hematopoietic stem/progenitor cells are increased by proliferation and differentiation (2019)
  • Author(s): Watanuki Shintaro、Kobayashi Hiroshi、Sorimachi Yuriko、Yamamoto Masamichi、Okamoto Shinichiro、Takubo Keiyo
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 印刷中 Issue: 1 Pages: 287-294
  • DOI: 10.1016/j.bbrc.2019.04.123
  • Peer Reviewed
• [Journal Article] Potential involvement of semaphorin 3A in maintaining intervertebral disc tissue homeostasis (2019)
  • Author(s): Mima Y, Suzuki S, Fujii T, Morikawa T, Tamaki S, Takubo K, Shimoda M, Miyamoto T, Watanabe K, Matsumoto M, Nakamura M, Fujita N.
  • Journal Title: J Orthop Res Volume: 37 Issue: 4 Pages: 972-980
  • DOI: 10.1002/jor.24258
  • Peer Reviewed / Open Access
• [Remarks] 国立国際医療研究センター研究所生体恒常性プロジェクト公式ウェブサイト
  • URL: https://takubolab.com/