Identification and Characterization of a Hematopoietic Stem Cell Niche in Spleen

• Project/Area Number: 23791093
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: MIZUKAMI Takuo 国立感染症研究所, その他部局等, 室長 (60415487)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 血液内科学 / 造血ニッチ / 髄外造血 / ATL / 造血幹細胞 / ニッチ / 微小環境 / 巨核球 / SDF-1 / Osteopontin / ニッチ細胞 / osteopontin / 成人T細胞白血病

Research Abstract

In adults, extrameduller hematopoiesis (EMH) can be induced by a hematological malignancy and some infectious diseases. However, the mechanism of HSCs regulation and niche cells at the EMH has not been well defined.
To reveal the mechanism of HSCs in the EMH, we utilized the c-fos knockout mouse (c-fos –/–) and CFU-S (colony forming unit-spleen) assay as an EMH model. First, to identify the main site of the HSC-niche in the EMH spleen, we performed HSC localization analysis using in situ hybridization of various HSC markers. Surprisingly, some CD34, Sca-1, c-kit, SCL/tal-1, and Tie-2 expressing cells were located near megakaryocyte like cells (MLCs). When we co-cultured HSCs with isolated MLCs, the numbers of HSC were significantly increased compare to with a liquid culture system. Taking these data together, we suggested that MLCs have the potential to support HSC proliferation.

Research Products

• [Journal Article] System vaccinology for the evaluation of influenza vaccine safety bymultiplex gene detection of novel biomarkers in a preclinical study and batch release test (2014)
  • Author(s): Mizukami T, Momose H, Kuramitsu M, Takizawa K, Araki K, Furuhata K, Ishii KJ, Hamaguchi I, Yamaguchi K
  • Journal Title: PLoS One Volume: (in press)
• [Journal Article] B-cell-intrinsic hepatitis C virus expression leads to B-cell-lymphomagenesis and induction of NF-κB signalling (2014)
  • Author(s): Kasama Y, Mizukami T, Kusunoki H, Peveling-Oberhag J, Nishito Y, Ozawa M, Kohara M, Mizuochi T, Tsukiyama-Kohara K
  • Journal Title: PLoS One Volume: 9(3)
• [Journal Article] B-cell-intrinsic hepatitis C virus expression leads to B-cell-lymphomagenesis and induction of NF-κB signalling (2014)
  • Author(s): Kasama Y, Mizukami T, Kusunoki H, Peveling-Oberhag J, Nishito Y, Ozawa M, Kohara M, Mizuochi T, Tsukiyama-Kohara K
  • Journal Title: PLoS One Volume: 9(3) Issue: 3 Pages: 91373-91373
  • DOI: 10.1371/journal.pone.0091373
  • Peer Reviewed / Open Access
• [Journal Article] Degenerate polymerase chain reaction strategy with DNA microarray for detection of multiple and various subtypes of virus during blood screening (2013)
  • Author(s): Takizawa K, Nakashima T, Mizukami T, Kuramitsu M, Endoh D, Kawauchi S, Sasaki K, Momose H, Kiba Y, Mizutani T, Furuta RA, Yamaguchi K, Hamaguchi I
  • Journal Title: Transfusion Volume: 53 Pages: 2545-55
• [Journal Article] Degenerate polymerase chain reaction strategy with DNA microarray for detection of multiple and various subtypes of virus during blood screening (2013)
  • Author(s): Takizawa K, Nakashima T, Mizukami T, Kuramitsu M, Endoh D, Kawauchi S, Sasaki K, Momose H, Kiba Y, Mizutani T, Furuta RA, Yamaguchi K, Hamaguchi I
  • Journal Title: Transfusion. Volume: 17 Issue: 10pt2 Pages: 17-17
  • DOI: 10.1111/trf.12193
  • Peer Reviewed
• [Journal Article] The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential (2012)
  • Author(s): Luc S, Luis TC, Boukarabila H, Macaulay IC, Buza-Vidas N, Bouriez-Jones T, Lutteropp M, Woll PS, Loughran SJ, Mead AJ, Hultquist A, Brown J, Mizukami T, Matsuoka S, Ferry H, Anderson K, Duarte S, Atkinson D, Soneji S, Domanski A, Farley A, Sanjuan-Pla A, Carella C, Patient R, de Bruijn M, Enver T, Nerlov C, Blackburn C, Godin I, Jacobsen SE
  • Journal Title: Nat Immunol Volume: 13 Pages: 412-9
• [Journal Article] Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia (2012)
  • Author(s): Kuramitsu M, Sato-Otsubo A, Morio T, Takagi M, Toki T, Terui K, Wang R, Kanno H, Ohga S, Ohara A, Kojima S, Kitoh T, Goi K, Kudo K, Matsubayashi T, Mizue N, Ozeki M, Masumi A, Momose H, Takizawa K, Mizukami T, Yamaguchi K, Ogawa S, Ito E, Hamaguchi I
  • Journal Title: Blood Volume: 119 Pages: 2376-84
• [Journal Article] The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential. (2012)
  • Author(s): Luc S, Luis TC,..., Mizukami T, Mats........, Patient R, de Bruijn M, Enver T, Nerlov C, Blackburn C, Godin I, Jacobsen SE.
  • Journal Title: Nature Immunology Volume: 13(4) Issue: 4 Pages: 412-419
  • DOI: 10.1038/ni.2255
  • Peer Reviewed
• [Journal Article] Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia. (2012)
  • Author(s): Kuramitsu M, Sato-Otsubo A, -省略-, Momose H, Takizawa K, Mizukami T, Yamaguchi K, Ogawa S, Ito E, Hamaguchi I.
  • Journal Title: Blood Volume: 119 Pages: 2376-2384
  • Peer Reviewed
• [Journal Article] Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia (2011)
  • Author(s): Kuramitsu M, Matsubara A, Morio T, Takagi M, Toki T, Terui K, RuNan W, Kanno H, Ohga S, Ohara A, Kitoh T, Sugita K, Kudo K, Matsubayashi T, Mizue N, Ozeki M, Masumi A, Momose H, Takizawa K, Mizukami T, Yamaguchi K, Ogawa S, Ito E, Hamaguchi I
  • Journal Title: Blood Volume: (in press) Issue: 10 Pages: 2376-84
  • DOI: 10.1182/blood-2011-07-368662
  • Peer Reviewed
• [Presentation] Identification of Leukemic stem cell and their niche in adult T cell leukemia (ATL) in the Tax-transgenic mouse model. (2012)
  • Author(s): Takuo Mizukami, Kazuya Takizawa, Madoka Kuramitsu, Haruka Momose, **Jumpei Yamazaki, ***William Hall, *Hideki Hasegawa, Kazunari Yamaguchi, Isao Hamaguchi
  • Organizer: 54th American Society of hematology
  • Place of Presentation: Atlanta, USA
• [Presentation] ATL癌幹細胞のニッチ形成過程における破骨細胞の役割 (2012)
  • Author(s): 水上拓郎、滝澤和也、狭間俊介、倉光球、百瀬暖佳、益見厚子、長谷川秀樹、浜口功
  • Organizer: 第74回 日本血液学会
  • Place of Presentation: 京都
• [Presentation] マウスモデルを用いたATL癌幹細胞及びそのニッチの解析 (2012)
  • Author(s): 水上 拓郎、滝澤 和也、山崎 淳平、倉光 球、百瀬 暖佳、益見 厚子、長谷川 秀樹、山口 一成、浜口 功
  • Organizer: 第154回 日本獣医学会
  • Place of Presentation: 岩手
• [Presentation] Identification of cancer stem cell niche in Adult T-Cell Leukemia / lymphoma (ATL) model mouse Tax-transgenic (Tax-Tg) mouse (2011)
  • Author(s): Takuo Mizukami, Kazuya Takizawa, Madoka Kuramitsu, Haruka Momose, **Jumpei Yamazaki, Atsuko Masumi, *Hideki Hasegawa, Kazunari Yamaguchi, Isao Hamaguchi
  • Organizer: 日本血液学会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] HTLV-1 Taxトランスジェニックマウスを用いたATL癌幹細胞及びそのニッチの同定 (2011)
  • Author(s): 水上拓郎、滝澤和也、山崎淳平、倉光球、百瀬暖佳、益見厚子、 長谷川秀樹、浜口功、山口一成
  • Organizer: 日本獣医学会
  • Place of Presentation: 大阪府立大学
• [Presentation] Identification and Characterization of Bone Marrow-derived Leukemic Stem Cells in a Tax-transgenic Mouse Model of Adult T-Cell Leukemia / Lymphoma. (2011)
  • Author(s): Mizukami T, Takizawa K, Kuramitsu M, Momose H, Mausmi A, Yamazaki J, Hasegawa H, Hall W, Yamaguchi K, Hamaguchi I
  • Organizer: XXV IACRLRD Symposium
  • Place of Presentation: 東京大学
• [Book] 医薬品の品質管理とウイルス安全性：ウイルス輸血・血液製剤と感染症 (2011)
  • Author(s): 山口一成、水上拓郎、野島清子
  • Total Pages: 301
  • Publisher: 文光堂