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在体干细胞中转录动态的单分子成像

Justin C Wheat^1,2, Yehonatan Sella³, Michael Willcockson¹

¹Department of Cell Biology, Albert Einstein College of Medicine, New York, NY, USA.

|June 26, 2020

概括

分子噪声驱动了干细胞的功能. 随机基因表达,而不是确定性过程,维持了造血干细胞的可塑性和强度.

科学领域:

分子生物学
干细胞生物学
系统生物学

背景情况:

分子噪声是生物系统的内在特性.
随机过程在维持组织平衡中的作用尚未完全理解.

研究的目的:

研究血造干细胞中关键基因的转录动态.
了解随机基因表达如何促进干细胞的强度和可塑性.

主要方法:

在小鼠的造血干细胞和原生细胞上进行单分子光RNA在位杂交 (smFISH).
对PU.1,Gata1和Gata2的转录动态的测量
集成smFISH与时间间隔显微镜和谱系分析.

主要成果:

不常见的随机转录突发导致对抗转录因子 (PU.1,Gata1,Gata2) 的联合表达.
干细胞克隆表现出与转录相关的后代,这表明"转录原始化"现象.
干细胞的状态转换最好通过随机,可逆动态模型.

结论:

随机基因表达对于保持干细胞的可塑性和强度至关重要.
被推断为决定性的细胞行为可能来自潜在的随机过程.
提出了一个模型,其中内在的基因表达噪声可以促进干细胞的维护.

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