Cell Reports (May 2020)
Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors
- Yuhki Nakatake,
- Shigeru B.H. Ko,
- Alexei A. Sharov,
- Shunichi Wakabayashi,
- Miyako Murakami,
- Miki Sakota,
- Nana Chikazawa,
- Chiaki Ookura,
- Saeko Sato,
- Noriko Ito,
- Madoka Ishikawa-Hirayama,
- Siu Shan Mak,
- Lars Martin Jakt,
- Tomoo Ueno,
- Ken Hiratsuka,
- Misako Matsushita,
- Sravan Kumar Goparaju,
- Tomohiko Akiyama,
- Kei-ichiro Ishiguro,
- Mayumi Oda,
- Norio Gouda,
- Akihiro Umezawa,
- Hidenori Akutsu,
- Kunihiro Nishimura,
- Ryo Matoba,
- Osamu Ohara,
- Minoru S.H. Ko
Affiliations
- Yuhki Nakatake
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Shigeru B.H. Ko
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Alexei A. Sharov
- Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6825, USA
- Shunichi Wakabayashi
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Miyako Murakami
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Miki Sakota
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Nana Chikazawa
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Chiaki Ookura
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Saeko Sato
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Noriko Ito
- DNA Chip Research, Tokyo 105-0022, Japan
- Madoka Ishikawa-Hirayama
- DNA Chip Research, Tokyo 105-0022, Japan
- Siu Shan Mak
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Lars Martin Jakt
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Tomoo Ueno
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Ken Hiratsuka
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Misako Matsushita
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Sravan Kumar Goparaju
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Tomohiko Akiyama
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Kei-ichiro Ishiguro
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Mayumi Oda
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Norio Gouda
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Akihiro Umezawa
- Department of Reproductive Biology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
- Hidenori Akutsu
- Department of Reproductive Biology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
- Kunihiro Nishimura
- Xcoo, Tokyo 113-0033, Japan
- Ryo Matoba
- DNA Chip Research, Tokyo 105-0022, Japan
- Osamu Ohara
- Kazusa DNA Research Institute, Chiba 292-0818, Japan
- Minoru S.H. Ko
- Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; Corresponding author
- Journal volume & issue
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Vol. 31,
no. 7
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.
