Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 transcrip-tional 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 overex-pressed, 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.

Original languageEnglish
Pages (from-to)6412-6417
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number16
DOIs
Publication statusPublished - 2013 Apr 16

ASJC Scopus subject areas

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    Hikichi, T., Matoba, R., Ikeda, T., Watanabe, A., Yamamoto, T., Yoshitake, S., Tamura-Nakano, M., Kimura, T., Kamon, M., Shimura, M., Kawakami, K., Okuda, A., Okochi, H., Inoue, T., Suzuki, A., & Masui, S. (2013). Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles. Proceedings of the National Academy of Sciences of the United States of America, 110(16), 6412-6417. https://doi.org/10.1073/pnas.1220200110