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使用CellTag-multi跨基因组模式捕获单细胞血统,揭示了命运特异性的基因调控变化

Kunal Jindal^1,2,3, Mohd Tayyab Adil^1,2,3, Naoto Yamaguchi^1,2,3

¹Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.

Nature biotechnology

|September 25, 2023

概括

通过捕获遗传条形码,CellTag-multi可以在多个单细胞检测中进行血统追踪. 这种方法揭示了细胞分化和重编程期间的基因调节变化,识别了Zfp281

科学领域:

分子生物学分子生物学
遗传学遗传学是一个
发展生物学发展生物学

背景情况:

细胞分化和重编程涉及复杂的基因调节网络.
目前的单细胞谱系追踪 (scLT) 方法通常依赖于转录分析,这限制了它们与其他单细胞分析的兼容性.

研究的目的:

开发一种与多种单细胞模式兼容的多功能血统追踪方法.
独立追踪克隆转录和表观基因组状态.
研究细胞分化和重编程中的基因调控机制.

主要方法:

开发了CellTag-multi,一种捕获遗传随机条形码的方法,表达为多基化转录.
应用CellTag-multi对单细胞RNA测序 (scRNA-seq) 和使用测序 (scATAC-seq) 进行转移酶可访问染色体的单细胞测试.
验证的CellTag-multi在小鼠血液形成和直接重编程纤维细胞到内皮原生体.

主要成果:

CellTag-multi成功启用了对转录和表观基因组细胞状态的独立克隆追踪.
在小鼠血液形成过程中,特征性原始细胞系的原始化.
在直接重编程过程中确定了在目标和非目标细胞命运中的核心调节程序,并揭示了Zfp281作为重编程结果的调节器,促进非目标介质细胞命运.

结论:

CellTag-multi是一种通用的谱系追踪方法,与各种单细胞模式兼容.
证明了CellTag-multi在发现分化和重编程中的命运规定的基因调控变化的实用性.
突出了Zfp281在重编程过程中指导细胞命运中的作用.

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