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リエゾンラボ研究会
発表内容

Title:
Core transcriptional network regulating cellular fate

Shinji Masui
Section of Molecular Biology and Cell Engineering, Research Institute, National Center for Global Health and Medicine Section Chief

Abstract:
A mammalian body consists of more than two hundred types of cells. It has been thought that the molecular mechanism making these differences involves transition of transcriptional network, which is mainly determined by combination of core transcription factors regulating relatively large number of target genes. In fact, recent reports have shown that forced expression of a set of transcription factors can induce cells-of-interest by trans-differentiation (e.g. iN and iCM cells), providing the direct evidences that core transcription factors play pivotal role in regulating differentiation. In future, identification of core transcription factors in many types of cells will promote the progress of developmental and systems biology. However, current techniques for the identification have fundamental problems.
In this seminar we will show the novel system to identify core transcription factors. By using this system in an example type of cells, we screened transcription factors having contribution to the transcriptional network regulating differentiation. A set of factors obtained, upon transduction into different type of cells, induced the cells similar to that used in the screening, demonstrating that these are core transcription factors. Unlike the other studies in which already-known factors based on previous reports were used for the induction, this system does not need a priori information of them; thereby this system can be applied to all type of cells in a mammalian body.

References:
Masui S. Pluripotency maintenance mechanism of embryonic stem cells and reprogramming. Int J Hematol. 91:360-372, 2010 (review)

Masui S et al. Rex1/Zfp42 is dispensable for pluripotency in mouse ES cells. BMC Dev Biol. 8:45, 2008

Masui S et al. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol. 9:625-635, 2007

Masui S et al. An efficient system to establish multiple embryonic stem cell lines carrying an inducible expression unit. Nucleic Acids Res. 33:e43, 2005