血小板生成素诱导胎肝CD34+ 造血干/祖细胞 增殖分化与周期蛋白表达的关系

Changes in cyclin expression during proliferation and differentiation of CD34+ cells derived from fetal liver induced by thrombopoietin

马东初  金伯泉  孙英慧  常奎忠  戴兵  初俊杰  刘亚革 

摘 要:为了解胚胎时期巨核细胞增殖分化特有的内在机制,本研究观察了在体外培养体系中,胎肝源CD34+造血干/祖细胞在血小板生成素(thrombopoietin,TPO)作用下增殖分化特征与相关周期蛋白B1、D1和D3表达及细胞内水平变化的关系。结果发现:(1)经12d培养后,TPO使胎肝源CD34+细胞数从1×05个细胞/ml增加到13.12±4.06×105个细胞/ml,CD41+细胞增加到了95%,CD34+细胞下降到了3%,大部分细胞的DNA倍性为2N,少数为4N,无大于4N巨核细胞,TPO对MegaCultTm-C胶原半固体培养体系中胎肝源CD34+细胞形成CFU-Mk集落产率的影响呈明显的剂量效应关系;(2)在整个培养期间,周期蛋白B1表达逐渐增加,并保持在一个高水平上,培养后期,高水平的周期蛋白B1出现在G1期细胞上;(3)周期蛋白D1和D3表达先增加,培养后期细胞内水平下降,且以G2期细胞为主。该结果提示:(1)TPO通过上调周期蛋白B1和在所有细胞周期时限上调周期蛋白D1和D3表达,促进巨核细胞祖细胞的增殖分化;(2)周期蛋白B1在G2+M期的持续高水平和周期蛋白D1和D3在G2+M期的水平下降,可能导致胎肝源巨核细胞核内有丝分裂延迟或阻滞。
关键词:周期蛋白; 血小板生成素; CD34+ 细胞; 巨核细胞
分类号:Q461; R329.2+8 文献标识码:A

 

基金项目:This work was supported by the Medical and Pharmaceutical Foundation of PLA (No.b96D003).
作者单位:马东初(沈阳军区总医院医学实验科, 沈阳 110015) 
     金伯泉(第四军医大学免疫教研室, 西安 710032) 
     孙英慧(沈阳军区总医院医学实验科, 沈阳 110015) 
     常奎忠(沈阳军区总医院医学实验科, 沈阳 110015) 
     戴兵(沈阳军区总医院医学实验科, 沈阳 110015) 
     初俊杰(沈阳军区总医院医学实验科, 沈阳 110015) 
     刘亚革(沈阳军区总医院医学实验科, 沈阳 110015) 

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收稿日期:2000年10月16日

修稿日期:2001年1月18日