从体质突变推断出正常人体血液的种群动态
Henry Lee-Six1, Nina Friesgaard Øbro2, Mairi S Shepherd2
1Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Nature
|September 7, 2018
概括
研究人员使用人体突变量化了人体造血干细胞的动态. 估计有5万到20万个活跃的干细胞产生白细胞.
科学领域:
- 血液学
- 遗传学
- 发育生物学
背景情况:
- 造血干细胞 (HSC) 对于整个生命中持续的血液产生至关重要.
- 在人类中直接量化HSC种群大小和动态是具有挑战性的.
- 了解HSC的克隆动态对于了解血液疾病和衰老至关重要.
研究的目的:
- 直接量化人类HSC的种群规模和生命周期动态.
- 重建人类造血系统的克隆结构和发育史.
- 使用自然发生的体突变作为追踪细胞系的标记.
主要方法:
- 从140个单细胞衍生的HSC和原生殖民地分析了129582个全基因组体变异.
- 应用种群遗传学的方法来重建基因关系和克隆动态.
- 从早期胚胎形成到成年期的细胞分裂的高分辨率追踪.
主要成果:
- 建立了一棵遗传树,揭示出细胞分裂起源于胃化之前的共同祖先.
- 在早期生活中显示HSC人口的稳定增长,在青春期达到平原.
- 估计活跃生产白细胞的数量在5万到20万之间.
- 观察到能够产生多系细胞的成年HSC克隆 (例如颗粒细胞,B淋巴细胞).
结论:
- 身体突变为重建人类器官克隆结构和细胞动态提供了强大的工具.
- 人类的HSC池在生命早期经历了显著的扩张,并在青春期稳定.
- 这项研究提供了对人类造血系统的长期动态和克隆组织的高分辨率见解.
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