造血干细胞的发育取决于血液的流动.
Trista E North1, Wolfram Goessling, Marian Peeters
1Stem Cell Program and Hematology/Oncology, Children's Hospital, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Cell
|May 20, 2009
概括
血流是脊椎动物胚胎发生过程中血造干细胞 (HSC) 形成的保守调节器. 氧化 (NO) 作为下游调解剂,对大动脉 - 淋巴体 - 中膜区域的高血压细胞发育至关重要.
科学领域:
- 发育生物学 发展生物学
- 血液形成 血液形成 血液形成
- 血管生物学 血管生物学
背景情况:
- 造血干细胞 (HSC) 对于血液形成至关重要,并在脊椎动物胚胎发生过程中起源于大动脉 - 淋巴体 - 中 (AGM) 区域.
- 准确的监管机制,规范HSC在年会的出现,仍然是一个活跃的研究领域.
研究的目的:
- 研究血流作为高血小板形成的保护调节者的作用.
- 为了确定下游信号通路参与流介导的HSC发展.
主要方法:
- 利用了带有化学血流调节器和影响血液循环的遗传突变 (静心突变) 的斑马鱼模型.
- 在斑马鱼中使用了氧化 (NO) 捐赠者和使用了morpholino knockdown 的 nos1 (nnos/enos).
- 检查了具有子宫内NO抑制和胚胎No3缺乏的小鼠模型.
主要成果:
- 斑马鱼胚胎的血液流动受损,表现出显著减少的HSCs.
- 没有捐赠者在流量受损的斑马鱼中拯救了HSC的发展,即使在循环开始之前给予.
- 斑马鱼的No1 Knockdown是细胞自主性的,小鼠的No3缺乏减少了造血集群和可移植的HSC.
结论:
- 血液流动是AGM区域中HSC发育的保守调节者.
- 氧化 (NO) 是一个关键的下游调解器在血液流量依赖的调节的HSC形成.
- 这项研究确立了血管动力学与血液形成最早阶段之间的直接联系.
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