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Transcription Factors Interfering with Dedifferentiation, Promote Differentiation

The research group led by researcher Takafusa Hikichi and Lecturer Shinji Masui elucidated that factors which interfere with dedifferentiation into iPS cells promote differentiation induction, as well as some of the dedifferentiation processes of differentiated cells. The findings were published online by the science journal Proceedings of the National Academy of Sciences on April 1, 2013.

Transcription factors (TFs) are able to promote cell differentiation, or conversely dedifferentiation and direct conversion of differentiated cells, by regulating the intracellular gene function. However, as the TFs in each cell are so diverse, it has been extremely difficult to clarify how the cell achieves its function or whether the differentiated state is maintained or not. 

Masui hypothesized that there should be decisive factors (core factors) that determines the direction of differentiation, while at the same time interfering with the cell dedifferentiation. Based on this, he developed an interference method to identify the core factors

In this study, the TFs specific to neural cells were selected and overexpressed, among which his team identified those that reduced the efficiency of dedifferentiation into iPS cells (i.e. interfere with iPS cell generation), as core factors. When these factors were introduced to hepatic cells, they were found to be capable of inducing neural cells. Similarly, when the core factors which interfered with dedifferentiation in hepatic cells were identified, it was found that they were the TFs already known for their induction activity into hepatic cells. 

These findings demonstrated that the hypothesis developed by Masui and his group was correct, elucidating that the core factors identified by the iPS interference method are able to directly convert cell types.

It is now anticipated that the use of this method makes it possible to unveil factors characterizing various differentiated cells, while helping to further understand each cell and advancing development of the differentiation induction method.
 

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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 and Shinji Masui
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