Identification and Characterization of a Hematopoietic Stem Cell Niche in Spleen

2013 Fiscal Year Final Research Report

• 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
• Keywords: 血液内科学 / 造血ニッチ / 髄外造血 / ATL

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) Pages: e91373
• [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] 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