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在单细胞分辨率下追踪造血干细胞的形成

Fan Zhou¹, Xianlong Li², Weili Wang³

¹State Key Laboratory of Proteomics, Translational Medicine Center of Stem Cells, 307-Ivy Translational Medicine Center, Laboratory of Oncology, Affiliated Hospital, Academy of Military Medical Sciences, Beijing 100071, China.

|May 27, 2016

概括

研究人员确定了前造血干细胞 (前造血干细胞) 的关键分子特征,这些特征对于生成最终造血干细胞 (造血干细胞) 至关重要. mTOR激活对于HSC的出现至关重要,而不仅仅是祖先的发展.

科学领域:

发育生物学
干细胞生物学
血液形成

背景情况:

造血干细胞 (HSC) 来自胚胎前体,包括血源性内皮细胞和造血前干细胞 (pre-HSC).
前HSCs的精确分子身份在很大程度上未被定义,这阻碍了对HSC发展的充分理解.
了解HSC前的生物学对于再生医学和HSC工程的发展至关重要.

研究的目的:

使用强大的表面标记物分离和描述新生前HSC.
阐明前HSCs的独特分子特征和功能性质.
调查拉巴胺素 (mTOR) 信号传递的机理性标在HSC出现中的作用.

主要方法:

通过单细胞启动的连续移植验证的高纯度前HSC的分离.
内皮细胞的单细胞RNA测序,CD45(-) 和CD45(+) 前HSC,以及胎儿肝脏HSC.
基于转录组数据的功能分析,以评估细胞周期异质性和信号通路.

主要成果:

前HSC表现出不同的转录机制,动脉特征,代谢状态,信号通路和转录因子网络.
拉巴胺素 (mTOR) 激活的机理性点对于HSC的出现至关重要,但对于造血原体则不至关重要.
通过转录组分析发现了前HSC细胞周期状态的显著异质性.

结论:

确定前HSC的核心分子特征为进一步研究提供了基础.
这项研究阐明了mTOR在从前体中产生HSC的不可或缺作用.
这些发现提供了关于HSCs in vivo逐步生成的见解,并为HSC工程提供了信息.

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