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混合血统状态的单细胞分析导致二进制细胞命运选择

Andre Olsson¹, Meenakshi Venkatasubramanian², Viren K Chaudhri¹

¹Division of Immunobiology and Center for Systems Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.

|September 1, 2016

概括

这项研究表明,混合血统状态对于细胞命运规范至关重要,涉及控制小鼠中性细胞和巨细胞发育的基因调控网络.

科学领域:

发育生物学
基因组学
细胞生物学

背景情况:

划分分层细胞状态和调节基因网络对于理解细胞类型规范至关重要.
单细胞RNA测序 (scRNA-seq) 是分析基因组状态和调节基因的强大工具.
具有共同表达的转录因子的混合血统状态可能是主要的发展潜力.

研究的目的:

在小鼠中确定中性细胞和巨细胞的等级基因组和调控状态.
在体内研究过渡状态的性质和细胞命运决定因素的动态.
确定参与细胞命运决策的关键调节基因和网络.

主要方法:

使用单细胞RNA测序 (scRNA-seq).
使用了一种新的分析工具,即代聚类和指导基因选择.
进行了克隆检测和遗传乱.

主要成果:

确定了表达干/原始基因和骨髓原始基因的常见混合系中间体.
发现了罕见的转基因稳定中间体,其干细胞/原始细胞程序已经崩,骨髓决定体表达低 (Irf8,Gfi1).
鉴定出Irf8和Gfi1是抵消基因调节网络的关键组成部分,它们的联合损失捕获了转移稳定的中间体.

结论:

在细胞命运规范过程中,混合血统状态是强制性的.
这些状态因动态不稳定而表现出不同的频率.
抗击基因调节网络决定了细胞命运.

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