结合ATP的磁带载体和HDL抑制了造血干细胞的增殖
Laurent Yvan-Charvet1, Tamara Pagler, Emmanuel L Gautier
1Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA. ly2159@columbia.edu
Science (New York, N.Y.)
|May 22, 2010
概括
缺乏ABCA1和ABCG1载体的小鼠显示白细胞和干细胞增加,导致疾病. 恢复高密度脂蛋白 (HDL) 水平扭转了这些影响,表明胆固醇运输和血细胞增殖之间存在联系.
科学领域:
- 心血管生物学 心血管生物学
- 血液形成 血液形成 血液形成
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 白细胞病,特别是单细胞病,与动脉样硬化有关.
- 导致白细胞数量升高的机制尚不清楚.
- 腺三酸盐结合盒 (ABC) 载体ABCA1和ABCG1对于胆固醇从巨细胞流出至关重要,并抑制动脉样硬化.
研究的目的:
- 研究ABCA1和ABCG1在调节造血干细胞和原生细胞群中的作用.
- 了解ABC转运体,白细胞体和动脉样硬化发育之间的联系.
主要方法:
- 产生和分析缺少ABCA1和ABCG1.1的小鼠.
- 骨髓移植的实验. 骨髓移植的实验.
- 血液造血干细胞和原生细胞 (LSK) 种群的评估.
- 评估白细胞症,骨髓扩散性疾病和动脉样硬化.
主要成果:
- 缺少ABCA1和ABCG1的小鼠表现出白细胞症,这是一个骨髓增殖性疾病,并扩展了Lin(-) Sca-1(+) Kit+ (LSK) 干细胞和原始细胞.
- 将Abca1(-/-)Abcg1(-/-) 骨髓移植到高密度脂蛋白 (HDL) 转基因小鼠中,抑制了LSK扩张和白细胞形成.
- 这种移植也逆转了骨髓增殖性疾病,但加速了动脉样硬化.
结论:
- ABCA1,ABCG1和HDL在造血干细胞和多潜原生细胞的增殖中起着关键的抑制作用.
- 这些干细胞和祖细胞种群的扩张与白细胞症和加速动脉样硬化直接相关.
- 这些发现在动脉样硬化背景下,建立了胆固醇外流途径和血液细胞生产调节之间的新鲜联系.
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