血造干细胞的血管的年龄依赖调节
Anjali P Kusumbe1, Saravana K Ramasamy1, Tomer Itkin2
1Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
Nature
|April 14, 2016
概括
激活血管细胞中的Notch信号扩大了骨中的造血干细胞. 这一途径使老化的骨血管再生,凸显了它在干细胞调节中的重要性.
科学领域:
- 骨生物学
- 血管生物学
- 干细胞
背景情况:
- 血管对于骨微环境,骨质生成和造血干细胞 (HSC) 基至关重要.
- 不完全了解形容器的特性及其与年龄相关的变化.
研究的目的:
- 调查内皮细胞中诺奇信号传递对HSC位扩张的作用.
- 确定内皮缺氧诱导因子 (HIF) 对血管位功能的影响.
- 评估与年龄相关的骨血管的恢复潜力.
主要方法:
- 使用小鼠模型研究内皮细胞中的Notch和HIF信号通路.
- 分析了CD31阳性毛细血管,PDGFRβ阳性周围细胞,动脉小细胞形成和干细胞因子水平的变化.
- 在年轻和老年小鼠中评估HSC位功能和血管特性.
主要成果:
- 内皮突信号促进高细胞扩张,增加毛细血管,PDGFRβ阳性细胞,动脉小细胞和干细胞因子.
- 内皮HIF信号部分诱导这些变化,但由于缺乏动脉化和PDGFRβ细胞扩张,无法增强利基功能.
- 老鼠骨血管缩,但可以通过激活内皮突信号恢复.
结论:
- 内皮细胞中的突信号是骨髓中HSC位大小和功能的关键调节器.
- 血管是复杂的,取决于年龄的微环境,涉及多种细胞类型和血管亚型.
- 向内皮突信号提供了一个潜在的策略来恢复老化的骨干细胞.
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