Chromosome stability by Rho-family small GTPase regulator in human embryonic stem cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26830088
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Masatoshi Ohgushi 国立研究開発法人理化学研究所, 多細胞システム形成研究センター, 上級研究員 (00462664)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ヒトES細胞 / 染色体安定性 / Rhoシグナル経路 / 多能性幹細胞 / ゲノム不安定性

Outline of Final Research Achievements

Human pluripotent stem cells, including embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), hold huge potential as reproductive resources for cell-therapies to treat a variety of diseases as well as for drug discovery. In this study, we explored biological function of ABR, a regulator of Rho-family small GTPases, in hESCs. We found that RNAi-mediated depletion of ABR caused several defects in mitotic process, leading to anueploidy transformation with a high frequency. This indicates that ABR has a pivotal role in mitotic fidelity and precise inheritance of genetic information in self-renewing hESCs. Since the emergence of genetically detrimental cells during long-term culture has been regarded to be a big obstacle for the practical utilization of hESCs/iPSCs, these results provide implications for developing hESC/iPSC culture methods that are better suited for human genetic studies and cell-based therapies.

Free Research Field

幹細胞生物学