Molecular mechanism of interference with iPSC induction

2014 Fiscal Year Final Research Report

• Project/Area Number: 24615004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Regenerative medicine
• Research Institution: Kyoto University
• Principal Investigator: MASUI Shinji 京都大学, iPS細胞研究所, 講師 (20342850)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: iPS細胞 / マスター転写因子 / ポリコーム

Outline of Final Research Achievements

We have previously shown that master transcription factors tend to interfere with dedifferentiation triggered by iPSC induction technique in a given cell type. In this study we sought to elucidate the mechanism of the interference. Overexpression of Yamanaka factors including Oct3/4 repressed genes highly expressed in somatic cells. This repression was thought to be their direct effect, as chromatin immunoprecipitation indicated direct binding of Oct3/4 on genes highly expressed in somatic cells. On the other hand, overexpression of a master transcription factor in somatic cells during iPSC induction inhibited this repression and decreased iPSC induction efficiency. These data indicate that this repression is necessary for iPSC induction, and that the interference can be seen as the antagonism between Yamanaka factors and master transcription factors on genes highly expressed in somatic cells.

Free Research Field

幹細胞生物学