骨髓原生菌群形成驱动紧急和白血病骨髓形成
Aurélie Hérault1, Mikhail Binnewies1, Stephanie Leong1
1The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Medicine, Division of Hematology/Oncology, University of California San Francisco, San Francisco, California 94143, USA.
Nature
|March 30, 2017
概括
在再生和白血病期间,粒细胞/巨原体 (GMP) 在骨髓中形成动态. 这些集群由利基信号和自我更新网络调节, 揭示了血液生产和疾病的新见解.
科学领域:
- 血液学
- 细胞生物学
- 发育生物学
背景情况:
- 骨髓骨髓分化的空间组织尚不清楚.
- 粒细胞/巨细胞 (GMP) 是血液生产中的关键细胞.
研究的目的:
- 在稳定状态,紧急状态和白血病骨髓形成过程中调查GMP的现场行为和空间组织.
- 确定控制GMP行为和差异化的监管机制.
主要方法:
- 在体内成像技术来跟踪小鼠模型的GMP行为.
- 对骨髓信号和基因表达网络的分析.
主要成果:
- 在稳定状态下,GMP分散;在再生过程中,它们形成局部差异化的动态集群.
- 再生GMP的形成由特定的骨髓信号和原始细胞自我更新网络 (Irf8和β-catenin) 控制.
- 在白血病中,由于持续的自我更新激活和缺乏抑制信号,GMP集群持续产生.
结论:
- GMPs在现场表现出动态集群行为,这对于调节紧急骨髓形成至关重要.
- 这种GMP集群机制在白血病中异常地被劫持,导致不受控制的增殖.
- 这项研究揭示了骨髓中骨髓分化的新空间时间组织.
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