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系统地绘制TF介导的细胞命运变化的图谱,通过聚合诱导与scRNA-seq和多omics方法相结合

Muyoung Lee¹, Qingqing Guo¹, Mijeong Kim¹

¹Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.

Genome research

|April 5, 2024

概括

我们开发了iTF-seq以识别可以改变细胞命运的转录因子 (TF). 这种方法揭示了迅速诱导分化的TF,并突出了参与细胞命运转换的GCM1和OTX2等先驱因素.

科学领域:

分子生物学分子生物学
发展生物学发展生物学
基因组学就是基因组学.

背景情况:

细胞功能是由涉及转录因子 (TFs) 和它们的DNA点的转录调节所支配的.
对于多个TF的细胞命运转换潜力,特别是在诱导性和单细胞环境中,人们的理解有限.

研究的目的:

引入和验证iTF-seq,这是一种用于识别能够在单细胞水平上诱导细胞命运变化的单个TFs的新方法.
通过使用多omics方法研究TF介导的细胞命运转换背后的机制.

主要方法:

开发iTF-seq用于随时间推移的转录组监测和鉴定诱导谱系的TFs.
使用生物化TFs进行多omics分析.
采用biochip-seq来识别先驱因素及其监管作用.

主要成果:

iTF-seq确定了多个TFs,这些TFs在一天内迅速触发转录组变化,表明小鼠胚胎干细胞在一天内发生分化.
表达强效TFs的细胞表现出细胞周期动态的改变和细胞死亡的增加.
鉴定出GCM1和OTX2是提高基因可访问性和激活谱系规范基因的先驱因素.

结论:

iTF-seq是绘制细胞命运转化途径的强大工具.
这项研究阐明了包括先驱因素在内的特定TFs在推动细胞命运快速变化的作用,并提供了对潜在分子机制的洞察.

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