Plasticity and diversity of hematopoietic stem cells

造血干细胞的可塑性和多样性

• 批准号: 13307028
• 负责人: NAKAUCHI Hiromitsu
• 金额: $ 34.53万
• 依托单位: THE UNIVERSITY OF TOKYO (2002-2003)University of Tsukuba (2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13307028/
• 关键词: hematopoietic stem cells; self-renewal; plasticity; 造血肝細胞; 血管内皮前駆細胞; lnk; アダプター分子; Gfi-1B; 肝幹細胞; 自己複製能; SP細胞; ABC transporter; bcrp-1; ABCG2

Hematopoietic stem cells (HSCs) are able to both self-renew and differentiate to multilineages. Clonal assay is therefore essential for their characterization. We have succeeded in a high degree of HSC purification and then established a clonal analysis for HSC potential after transplantation of one HSC into a mouse. Using this method, this study addressed two major issues regarding their plasticity and self-renewal limitation. We examined the distribution of HSC-derived cells in a variety of organs and tissues after transplantation of single HSCs isolated from GFP transgenic mice. GFP+ cells were widely distributed in various tissues, but most of them appeared to be positive for blood cell markers, and very few cells were considered to have non-hematopoietic phenotypes. These data suggest that HSCs have too little plasticity to contribute the regeneration of non-hematopoietic tissues. The clonal analysis of HSC self-renewal revealed that degrees to which they self-renew vary and that their self-renewal is extensive, but limited. It was further clarified that Bmi-1 belonging to Polycomb group genes is one of the molecules that restrict this capacity and that the signal adaptor protein, Lnk is strongly involved in events where HSCs decide to either self-renew or differentiate. Their precise mechanisms are under investigation.

造血干细胞（HSC）能够自我更新并分化为多谱系。因此，克隆测定对于它们的表征至关重要。我们成功地进行了 HSC 的高度纯化，然后将一个 HSC 移植到小鼠体内后建立了 HSC 潜力的克隆分析。使用这种方法，本研究解决了有关其可塑性和自我更新限制的两个主要问题。我们检查了从 GFP 转基因小鼠中分离的单个 HSC 移植后，HSC 衍生细胞在各种器官和组织中的分布。 GFP+细胞广泛分布于各种组织中，但大多数表现为血细胞标志物阳性，极少数细胞被认为具有非造血表型。这些数据表明，HSC 的可塑性太低，无法促进非造血组织的再生。 HSC自我更新的克隆分析表明，它们的自我更新程度各不相同，并且它们的自我更新是广泛的，但也是有限的。进一步阐明，属于 Polycomb 组基因的 Bmi-1 是限制这种能力的分子之一，并且信号接头蛋白 Lnk 强烈参与 HSC 决定自我更新或分化的事件。它们的精确机制正在研究中。

项目成果

Tahara-H.S, Sudo K., Ema H., Miyoshi H., Nakauchi H.: "Lentiviral Vector-Mediated Transduction of Murine CD34-Hematopoietic Stem Cells."Exp.Hematology.. 30. 11-17 (2002)

Tahara-H.S、Sudo K.、Ema H.、Miyoshi H.、Nakauchi H.：“慢病毒载体介导的小鼠 CD34 造血干细胞的转导。”Exp.Hematology.. 30. 11-17 (2002)

Hiromitsu Nakauchi, Kazuhiro Sudo, Hideo Ema: "Quantitative assessment of the stem cell self renewal capacity. Stem Cell III."Ann N Y Acad Sci. 938. 18-25 (2001)

Hiromitsu Nakauchi、Kazuhiro Sudo、Hideo Ema：“干细胞自我更新能力的定量评估。干细胞 III。”Ann N Y Acad Sci。

Yoshida F, Matsumura A, Shibata Y, Yamamoto T, Nakauchi H, Okumura M, Nose T.: "Cell cycle dependence of boron uptake from two boron compounds used for clinical neutron capture therapy."Cancer Lett.. 187. 135-141 (2002)

Yoshida F、Matsumura A、Shibata Y、Yamamoto T、Nakauchi H、Okumura M、Nose T.：“用于临床中子捕获治疗的两种硼化合物吸收硼的细胞周期依赖性。”Cancer Lett.. 187. 135-141

Tsutomu Motohashi, Yukio Nakamura, Mitsujiro Osawa, Takashi Hiroyama, Atsushi Iwama, Akira Shibuya, Hiromitsu Nakauchi.: "Increased cell surface expression of C-terminal truncated erythropoietin receptors in polycythemia."European Journal of Haematology.

Tsutomu Motohashi、Yukio Nakamura、Mitsujiro Osawa、Takashi Hiroyama、Atsushi Iwama、Akira Shibuya、Hiromitsu Nakauchi.：“红细胞增多症中 C 端截短的促红细胞生成素受体的细胞表面表达增加。”欧洲血液学杂志。

Suzuki.A.et al.: "Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver."Journal of Cell Biology. 156. 173-184 (2002)

Suzuki.A.等人：“发育中肝脏中自我更新多能干细胞的克隆鉴定和表征。”细胞生物学杂志。