Differentiation of hematopoietic stem cell and myeloid populations by ATP is modulated by cytokines.
Differentiation of hematopoietic stem cell and myeloid populations by ATP is modulated by cytokines.
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DOI：
10.1038/cddis.2011.49
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发表时间：
2011-06-02
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞外核苷酸正在成为包括造血系统在内的多种组织中炎症、细胞增殖和分化的重要调节剂。在这项研究中，ATP的作用进行了调查，在小鼠造血。ATP能够降低造血干细胞（HSC）、普通髓系祖细胞和粒细胞-巨噬细胞祖细胞（GMP）的百分比，而向巨核细胞-红系祖细胞的分化不受影响。此外，在小鼠体内给予ATP减少了GMP的数量，但增加了Gr-1+Mac-1+骨髓细胞的数量。ATP还诱导亚致死剂量照射小鼠HSC增殖率增加，Notch表达减少，HSC介导的骨髓重建受损。此外，ATP引起的影响被苏拉明，一种P2受体拮抗剂，和BAPTA，一种细胞内Ca ~（2+）螯合剂抑制。我们进一步研究了细胞因子的存在是否可以调节观察到的ATP诱导的分化。在ATP刺激之前用细胞因子（干细胞因子、白细胞介素-3和粒细胞-单核细胞集落刺激因子）处理细胞导致长期骨髓培养物中ATP依赖性分化减少，从而恢复HSC重建造血的能力。因此，我们的数据表明，ATP诱导小鼠HSC分化为髓系，这种作用可以通过细胞因子调节。
Extracellular nucleotides are emerging as important regulators of inflammation, cell proliferation and differentiation in a variety of tissues, including the hematopoietic system. In this study, the role of ATP was investigated during murine hematopoiesis. ATP was able to reduce the percentage of hematopoietic stem cells (HSCs), common myeloid progenitors and granulocyte–macrophage progenitors (GMPs), whereas differentiation into megakaryocyte–erythroid progenitors was not affected. In addition, in vivo administration of ATP to mice reduced the number of GMPs, but increased the number of Gr-1+Mac-1+ myeloid cells. ATP also induced an increased proliferation rate and reduced Notch expression in HSCs and impaired HSC-mediated bone marrow reconstitution in sublethally irradiated mice. Moreover, the effects elicited by ATP were inhibited by suramin, a P2 receptor antagonist, and BAPTA, an intracellular Ca2+ chelator. We further investigated whether the presence of cytokines might modulate the observed ATP-induced differentiation. Treatment of cells with cytokines (stem cell factor, interleukin-3 and granulocyte–monocyte colony stimulator factor) before ATP stimulation led to reduced ATP-dependent differentiation in long-term bone marrow cultures, thereby restoring the ability of HSCs to reconstitute hematopoiesis. Thus, our data suggest that ATP induces the differentiation of murine HSCs into the myeloid lineage and that this effect can be modulated by cytokines.
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影响因子：
3.5
作者：
Communi, D;Janssens, R;Boeynaems, JM
通讯作者：
Boeynaems, JM
影响因子：
5.6
作者：
Leon, Carlos M. M. P.;Barbosa, Christiano M. V.;Paredes-Gamero, Edgar J.
通讯作者：
Paredes-Gamero, Edgar J.
DOI：
10.1084/jem.20050967
发表时间：
2005-12-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Passegué E;Wagers AJ;Giuriato S;Anderson WC;Weissman IL
通讯作者：
Weissman IL
影响因子：
20.3
作者：
Nilsson, SK;Johnston, HM;Coverdale, JA
通讯作者：
Coverdale, JA
影响因子：
5.6
作者：
Giltaire, Severine;Lambert, Sylviane;Poumay, Yves
通讯作者：
Poumay, Yves