Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6825, USA.
Cell Rep. 2020 May 19;31(7):107655. doi: 10.1016/j.celrep.2020.107655.
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.
转录因子（TFs）在决定细胞状态方面起着至关重要的作用，但我们对 TFs 与细胞状态之间的因果关系的理解还很有限。在这里，我们通过大规模操纵单个 TFs，系统地研究了人类多能胚胎干细胞（hESCs）的状态变化。我们建立了 2135 个人类胚胎干细胞系，代表 714 个可诱导的 doxycycline（Dox）基因中的三个克隆，每个克隆包含 481 个 TFs，并且在 Dox 存在或不存在 48 小时后，获得了 26998 个微观细胞图像和 2174 个转录组数据集-RNA 测序（RNA-seq）或微阵列。有趣的是，这些 TFs 会干扰几乎所有基因的表达，包括位于异染色质区域的基因。TFs 还具有诱导 hESCs 分化为特定细胞谱系的能力。这些分析有助于对 TFs 进行分类，并确定特定的 TFs 集合，以指导 hESC 分化为所需的细胞类型。
