Molecular discovery research targeting cardiac remodeling using multi-directional transcriptional profiling and therapeutic application

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860558
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Osaka University
• Principal Investigator: Higo Shuichiro 大阪大学, 医学(系)研究科(研究院), 助教 (00604034)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 心不全 / 心臓リモデリング / 高速シークエンサー

Outline of Final Research Achievements

For exploratory research aimed at regulatory mechanisms underlying pathological proliferation of non-cardiomyocytes during the progression of cardiac remodeling, we applied H3K4me3 mapping and RNA-sequence to pressure-overloaded hearts of mice. From the combination of Epigenomics and Transcriptomics, we identified a set of genes involved in interstitial fibrosis, and identidied a transcription factor specifically expressed in interstitial cardiac fibroblasts. The transcription factor is expressed in a limited population of fbroblasts and required for reactive proliferation. Next, to clarify unknown regulating mechanisms underlying hypertrophic response in cardiomyocytes, we combined quantitative RNA imaging and ChIP-sequence and identified a negative regulator of cardiomyocyte hypertropy. Our exploratory analysis identifies pathologically relevant molecules using a combination of multidimensional datasets and suggests the usefulness of TransOmics in cardiovascular pathophysiology.

Free Research Field

心不全