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生体防御のメカニズム 造血幹細胞の分化と自己複製の制御機構

研究報告コード R990004240
掲載日 2001年2月6日
研究者
  • 中内 啓光
研究者所属機関
  • 筑波大学基礎医学系
研究機関
  • 筑波大学基礎医学系
報告名称 生体防御のメカニズム 造血幹細胞の分化と自己複製の制御機構
報告概要 マウス骨髄ならびに胎仔肝臓中の造血幹細胞の純化法を確立し、クローナルな解析を行うことが可能になった。また、造血幹細胞の分化と増殖の様式をクローナルに詳しく解析することにより分化の方向性の決定が必ずしも無作為ではないことを示す最初の手がかりが得られた。具体的には、Paired-daughter cell実験法による個々の造血幹細胞の分化の様式の解析を行い、娘細胞由来のコロニーの両方に特定の血球細胞が出現する頻度を計算し、期待値と実測値と比較すると芽球、巨核球、好酸球が有意に高い頻度で娘細胞間コロニーに存在することが明らかになった。これらのデータは造血幹細胞からの血液細胞の分化が完全にはストキャスティックに起こっているのではないことを強く示唆するものである。造血幹細胞の細胞周期制御機構についても基礎的な解析が進み、造血幹細胞の98%以上の細胞がG0G1期にあること、さらに長期間にわたるBrdUの取り込み実験から、全造血幹細胞の2%だけが造血に関わっているのではなく、骨髄中で幹細胞全体が数週間に1回の頻度でゆっくりと増殖していることを明らかにした。
研究分野
  • 遺伝子の複製
  • 生体防御と免疫系一般
  • 細胞生理一般
  • 細胞分裂・増殖
  • 造血系
関連発表論文 1 Naoko Minegishi, Jun Ohta, Naruyoshi Suwabe, Hiromitsu Nakauchi, Hajime Ishihara, Norio Hayashi, and Masayuki Yamamoto. Alternative Promoters Regulate Transcription of the Mouse GATA-2 Gene. The Journal of Biological Chemistry. 273: 3625-3634, 1998
2. Dong Ku Kim, Masaharu Kojima, Takashi Fukushima, Masayuki Miyasaka,and Hiromitsu Nakauchi. Engraftment of human myelodysplastic syndrome derived cell line in transgenic severe combined immunodeficient (TG-SCID) mice expressing human GM-CSF and IL-3. Eur. J. Haematol. 61: 93-99, 1998.
3. Sinya Tamura, Takehiko Sugawara, Yayoi Tokoro, Hideki Taniguchi, Katashi Fukao, Hiromitsu Nakauchi and Yousuke Takahama. Expression and function of c-Met, a receptor for hepatocyte growth factor, during thymocyte development. Scand. J. Immunol. 47: 296-301, 1998.
4. Kazuhiko Igarashi, Hideto Hoshino, Akihiko Muto, Naruyoshi Suwabe, Shinichi Nishikawa, Hiromitsu Nakauchi, and Masayuki Yamamoto. Multivalent DNA Binding Complex Generated by Small Maf and Bach1 as a Possible Biochemical Basis for β- Globin Locus Control Region Complex. The Journal of Biological Chemistry. The Journal of Biological Chemistry. 273: 11783-11790, 1998.
5. Takashi Fukushima, Ryo Sumazaki, Kazuhiko Koike, Masahiro Tsuchida, Akira Matsui, Hiromitsu Nakauchi. Multicolor Flow-cytometoric, Morphologic, and Clonogenic Analysis of Marror CD10-Positive Cells in Children With Leukemia in Remmision or Nonmalignat Diseases. Journal of Pediotric Hematology / Oncology. 20: 222-228, 1998.
6. Takehiko Sugawara, Vincenzo Di Bartolo, Tadaaki Miyazaki, Hiromitsu Nakauchi, Oreste Acuto and Yousuke Takahama. An improved retroviral gene-transfer technique demonstrates inhibition of CD4-CD8- thymocyte development by kinase-inactive ZAP-70. Journal of Immunology. 161: 2888-2894, 1998.
7. Akihiko Muto, Hideto Hoshino, Linda Madisen, Nobuaki Yanai, Masuo Obinata, Hajime Karasuyama, Norio Hayashi, Hiromitsu Nakauchi, Masayuki Yamamoto, Mark Groudine, and Kazuhiko Igarashil. Identification of Bach2 as a B cell-specific partner for small Maf proteins that negatively regulates the immunoglobulin heavy chain gene 3' enhancer. EMBO J. 17:5734-5743, 1998.
8. Yayoi Tokoro, Takehiko Sugawara, Hiroyuki Yaginuma, Hiromitsu Nakauchi, Cox Terhorst, Baoping Wang, and Yousuke Takahama. A Mouse Carrying Genetic Defect in the Choice Between T and B lymphocytes. Journal of Immunology. 161: 4591-4598, 1998.
9. Yukio Nakamura, Hina Takano, Mitsujiro Osawa, Takashi Tomita, Dong-Ku Kim, Masaharu Kojima, Tsutomu Motohashi, Sousuke Miyoshi, Takashi Hiroyama, Yasuhito Tokumoto, Hiromitsu Nakauchi. Impaired erythropoiesis in transgenic mice overexpressing a trancated erythropoietin receptor. Exp. Hematology. 26: 1105-1110, 1998.
10. H. Taniguchi, A. Sugioka, M. Morita, A. Hasumi, Y. Takada, K. Fukunaga, K. Yuzawa, M. Otsuka, K. Fukao, and H. Nakauchi. Is Donor-Derived Long-Term and Multilineage Hematopoiesis Established After Liver Transplantation? Tranplantation Proceedings. 30, 3865-3866, 1998.
11. Hiromitsu Nakauchi. The hematopoietic stem cells. Are they CD34 positive or CD34 negative? News and Views. Nature Medicine 4:1009-1010, 1998
12. Hiromitsu Nakauchi. Further characterization of the CD34-low-negative mouse hematopoietic stem cell. The Hematopoietic Stem Cell. edited by Shirkis, Orlic and Kantz. Academic Press 872: 57-70, 1999
13. Kim DK, Fujiki Y, Fukushima T, Ema H, Shibuya A and Nakauchi H : Comparison of hematopoietic activities of human bone marrow and umbilical cord blood CD34 positive and negative cells. Stem Cells 17:286-94, 1999
14. Yamaguchi T, Watanabe N, Nakauchi H and Koito A : Human immunodeficiency virus type 1 Vpr modifies cell proliferation via multiple pathways. Microbiol Immunol 43:437-47, 1999
15. Matsuda K, Koguma M, Okuyama R, Nakazawa T, Matsuzaki Y, Nakauchi H, Yanai N, Terasaki T and Obinata M : A novel stromal cell-dependent B lymphoid stem-like cell line that induces immunoglobulin gene rearrangement. J Biochem (Tokyo) 125:602-12, 1999
16. Taniguchi H, Kondo R, Suzuki A, Zheng Y, Ito S, Takada Y, Fukunaga K, Seino K, Yuzawa K, Otsuka M, Fukao K, Yoshiki A, Kusakabe M and Nakauchi H : Evidence for the presence of hepatic stem cells in the murine fetal liver. Transplant Proc 31:454, 1999
17. Apostolou I, Takahama Y, Belmant C, Kawano T, Huerre M, Marchal G, Cui J, Taniguchi M, Nakauchi H, Fournie JJ, Kourilsky P and Gachelin G : Murine natural killer T(NKT) cells [correction of natural killer cells] contribute to the granulomatous reaction caused by mycobacterial cell walls [published erratum appears in Proc Natl Acad Sci U S A 1999 Jun 22;96(13):7610]. Proc Natl Acad Sci U S A 96:5141-6, 1999
18. Nakauchi H, Takano H, Ema H and Osawa M : Further characterization of CD34-low/negative mouse hematopoietic stem cells. Ann N Y Acad Sci 872:57-66; discussion 66-70, 1999
19. Murata H, Nakauchi H and Sumida T : Microchimerism in Japanese women patients with systemic sclerosis. Lancet 354:220, 1999
20. Saitoh S, Momoi MY, Yamagata T, Nakauchi H, Nihei K and Fujii M : Single-cell analysis of mitochondrial DNA in patients and a carrier of the tRNA(Leu)(UUR) gene mutation. J Inherit Metab Dis 22:608-14, 1999
21. Shibuya K, Lanier LL, Phillips JH, Ochs HD, Shimizu K, Nakayama E, Nakauchi H and Shibuya A : Physical and functional association of LFA-1 with DNAM-1 adhesion molecule. Immunity 11:615-23, 1999
22. Taniguchi H, Suzuki A, Zheng Y, Kondo R, Takada Y, Fukunaga K, Seino K, Yuzawa K, Otsuka M, Fukao K and Nakauchi H : Usefulness of flow-cytometric cell sorting for enrichment of hepatic stem and progenitor cells in the liver. Transplant Proc 32:249-51, 2000
23. Ema H and Nakauchi H : Expansion of hematopoietic stem cells in the developing liver of a mouse embryo. Blood 95:2284-8, 2000
24. Kaneta M, Osawa M, Sudo K, Nakauchi H, Farr AG and Takahama Y : A role for pref-1 and HES-1 in thymocyte development. J Immunol 164:256-64, 2000
25. Onodera, M. and Sakiyama Y. Adenosine deaminase deficiency as the first target disorder in gene therapy. Expant Opinion on Investigational Drugs. 9:543-549, 2000.
研究制度
  • 戦略的基礎研究推進事業、研究領域「生体防御のメカニズム」研究代表者 中内 啓光(筑波大学基礎医学系)/科学技術振興事業団
研究報告資料
  • 中内 啓光. 生体防御のメカニズム 造血幹細胞の分化と自己複製の制御機構. 戦略的基礎研究推進事業 平成10年度 研究年報,1999. p.211 - 213.

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