Title |
Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles
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Published in |
Proceedings of the National Academy of Sciences of the United States of America, April 2013
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DOI | 10.1073/pnas.1220200110 |
Pubmed ID | |
Authors |
Takafusa Hikichi, Ryo Matoba, Takashi Ikeda, Akira Watanabe, Takuya Yamamoto, Satoko Yoshitake, Miwa Tamura-Nakano, Takayuki Kimura, Masayoshi Kamon, Mari Shimura, Koichi Kawakami, Akihiko Okuda, Hitoshi Okochi, Takafumi Inoue, Atsushi Suzuki, Shinji Masui |
Abstract |
Transcription factors (TFs) are able to regulate differentiation-related processes, including dedifferentiation and direct conversion, through the regulation of cell type-specific transcriptional profiles. However, the functional interactions between the TFs regulating different transcriptional profiles are not well understood. Here, we show that the TFs capable of inducing cell type-specific transcriptional profiles prevent the dedifferentiation induced by TFs for pluripotency. Of the large number of TFs expressed in a neural-lineage cell line, we identified a subset of TFs that, when overexpressed, strongly interfered with the dedifferentiation triggered by the procedure to generate induced pluripotent stem cells. This interference occurred through a maintenance mechanism of the cell type-specific transcriptional profile. Strikingly, the maintenance activity of the interfering TF set was strong enough to induce the cell line-specific transcriptional profile when overexpressed in a heterologous cell type. In addition, the TFs that interfered with dedifferentiation in hepatic-lineage cells involved TFs with known induction activity for hepatic-lineage cells. Our results suggest that dedifferentiation suppresses a cell type-specific transcriptional profile, which is primarily maintained by a small subset of TFs capable of inducing direct conversion. We anticipate that this functional correlation might be applicable in various cell types and might facilitate the identification of TFs with induction activity in efforts to understand differentiation. |
X Demographics
Geographical breakdown
Country | Count | As % |
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France | 1 | 25% |
United States | 1 | 25% |
Canada | 1 | 25% |
Japan | 1 | 25% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 50% |
Scientists | 2 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 3% |
Japan | 3 | 2% |
Germany | 1 | <1% |
France | 1 | <1% |
Iran, Islamic Republic of | 1 | <1% |
Portugal | 1 | <1% |
Saudi Arabia | 1 | <1% |
Spain | 1 | <1% |
Unknown | 143 | 92% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 41 | 26% |
Student > Ph. D. Student | 32 | 21% |
Professor > Associate Professor | 17 | 11% |
Student > Master | 16 | 10% |
Student > Bachelor | 8 | 5% |
Other | 27 | 17% |
Unknown | 15 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 83 | 53% |
Biochemistry, Genetics and Molecular Biology | 26 | 17% |
Medicine and Dentistry | 21 | 13% |
Engineering | 3 | 2% |
Computer Science | 2 | 1% |
Other | 6 | 4% |
Unknown | 15 | 10% |