The effect of bleeding on hematopoietic stem cell cycling and self-renewal
The effect of bleeding on hematopoietic stem cell cycling and self-renewal
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DOI：
10.1089/scd.2007.0017
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发表时间：
2007-10-01
影响因子：
4
通讯作者：
Weissman, Irving L.
中科院分区：
文献类型：
--
作者：
Cheshier, Samuel H.;Prohaska, Susan S.;Weissman, Irving L.
造血干细胞（HSC）分裂并产生更多的定型祖细胞，最终产生所有的血细胞谱系。HSC可以在体外和体内通过刺激性细胞因子诱导进入细胞周期，在体内通过用辐射或化疗剂消融骨髓（BM）细胞来诱导进入细胞周期。虽然已经假设HSC增殖率随着正常造血应激（如感染或出血）而增加，但是该假设从未被直接检验。通过细胞表面表型c-kit（+）、Thy1.1（lo）、Sca-1（+）、Lineage（neg/lo）前瞻性分析HSC的能力，使我们能够详细检查出血对HSC细胞周期动力学的影响。我们的研究结果首次表明，骨髓和脾脏中的HSC增殖和自我更新，以响应小鼠尾静脉出血。当出血后转移红细胞时，这种反应受到抑制，但当转移白色细胞时，这种反应不受抑制。因此，HSC增殖的调节剂可以感知并响应红细胞水平。
Hematopoietic stem cells (HSCs) divide and give rise to more committed progenitors, which ultimately produce all lineages of blood cells. HSCs can be induced to enter the cell cycle in vitro and in vivo by stimulatory cytokines and in vivo by ablation of bone marrow ( BM) cells with irradiation or chemotherapeutic agents. Although it has been postulated that rates of HSC proliferation increase with normal hematopoietic stresses, such as infection or hemorrhage, this hypothesis has never been directly tested. The ability to analyze HSCs prospectively by cell-surface phenotype c-kit(+), Thy1.1(lo), Sca-1(+), Lineage(neg/lo) has allowed us to perform a detailed examination of the effects of bleeding on the cell cycle kinetics of HSCs. Our results demonstrate for the first time that HSCs in both the BM and the spleen proliferate and self-renew in response to tail-vein bleeding in mice. This response was suppressed when red blood cells, but not when white blood cells, were transferred after bleeding. Thus, regulators of HSC proliferation can sense and respond to red blood cell levels.