Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors
Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors
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DOI：
10.1016/j.celrep.2020.107655
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发表时间：
2020-05-19
期刊：
影响因子：
8.8
通讯作者：
Ko, Minoru S. H.
中科院分区：
文献类型：
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作者：
Nakatake, Yuhki;Ko, Shigeru B. H.;Ko, Minoru S. H.
转录因子在决定细胞状态方面起着关键作用，但我们对转录因子和细胞状态之间的因果关系的了解有限。在这里，我们系统地研究了大规模操作单个转录因子后人类多能胚胎干细胞(HESCs)的状态变化。我们建立了2,135个hESC系，分别代表714个多西环素(Dox)诱导基因的3个克隆，包括481个TF，并在存在或不存在Dox 48小时后获得了26,998个显微细胞图像和2,174个转录组数据集-RNA测序(RNA-seq)或微阵列。有趣的是，几乎所有基因的表达，包括位于异染色质区域的基因，都受到这些因子的干扰。转铁蛋白还具有诱导hESCs分化为特定细胞系的能力。这些分析有助于提供一种方法来对转录因子进行分类，并识别特定的转录因子集合，以指导hESC分化为所需的细胞类型。
Transcription factors (TFs) play a pivotal role in determining cell states, yet our understanding of the causative relationship between TFs and cell states is limited. Here, we systematically examine the state changes of human pluripotent embryonic stem cells (hESCs) by the large-scale manipulation of single TFs. We establish 2,135 hESC lines, representing three clones each of 714 doxycycline (Dox)-inducible genes including 481 TFs, and obtain 26,998 microscopic cell images and 2,174 transcriptome datasets-RNA sequencing (RNA-seq) or microarrays-48 h after the presence or absence of Dox. Interestingly, the expression of essentially all the genes, including genes located in heterochromatin regions, are perturbed by these TFs. TFs are also characterized by their ability to induce differentiation of hESCs into specific cell lineages. These analyses help to provide a way of classifying TFs and identifying specific sets of TFs for directing hESC differentiation into desired cell types.