Transcriptional analysis of SMC differentiation and de-differentiation using iPS cells and the medical application of arterial sclerosis

2015 Fiscal Year Final Research Report

• Project/Area Number: 23790840
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: University of the Ryukyus (2014-2015); The University of Tokyo (2011-2013)
• Principal Investigator: HAYAKAWA Tomoko 琉球大学, 医学(系)研究科(研究院), 助教 (30420821)
• Project Period (FY): 2011-04-28 – 2016-03-31
• Keywords: 血管平滑筋細胞 / ヒストン修飾 / 細胞分化

Outline of Final Research Achievements

Smooth muscle cells (SMCs) play a pivotal role in development of vascular disease, in which they markedly change their phenotypes. We established a novel in vitro SMC differentiation system using iPS cells. Using this system we assessed if histone modifying enzymes (HMEs) might be involved in SMC differentiation and phenotypic modulation. We found a number of HMEs were differentially regulated during SMC differentiation. We also found that expression of many HMEs was altered in phenotypically modulated SMCs in the mouse carotid ligation model. Based on these results we identified 10 HMEs that might be involved in the control of SMC phenotype and systematically knocked down them in SMCs. Among the HMEs tested HME-A was upregulated by phenotypic modulation and its knockdown markedly augmented the SMC differentiation marker genes, suggesting that HME-A is crucially involved in phenotypic modulation of SMCs.

Free Research Field

血管生物学