1. Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors
- Author
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Tomohiko Akiyama, Lars Martin Jakt, Chiaki Ookura, Misako Matsushita, Miki Sakota, Kunihiro Nishimura, Yuhki Nakatake, Saeko Sato, Miyako Murakami, Minoru S.H. Ko, Kei-ichiro Ishiguro, Nana Chikazawa, Noriko Ito, Sravan Kumar Goparaju, Akihiro Umezawa, Norio Gouda, Shigeru B. H. Ko, Osamu Ohara, Alexei A. Sharov, Hidenori Akutsu, Siu Shan Mak, Madoka Ishikawa-Hirayama, Ken Hiratsuka, Shunichi Wakabayashi, Ryo Matoba, Mayumi Oda, and Tomoo Ueno
- Subjects
0301 basic medicine ,Cell type ,Heterochromatin ,Cellular differentiation ,genetic processes ,Cell ,Computational biology ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,conditional induction ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,transcription factors ,medicine ,Humans ,natural sciences ,lcsh:QH301-705.5 ,Transcription factor ,Gene ,fungi ,human embryonic stem cells ,Embryonic stem cell ,cell differentiation ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,Single-Cell Analysis ,transcriptome ,030217 neurology & neurosurgery - Abstract
Summary 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.
- Published
- 2020
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