The amounts of gene expressions are diverse among each organ and moreover the patterns of gene expressions drastically change for adapting to various stimulations from outside. Such an organ-specific gene expression is regulated by the “enhancer” located far from the gene. As the enhancers can induce organ-specific gene expressions, gene therapies targeting the enhancers are developing in late years.
The natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are well-known biomarkers that are strongly induced during heart failure and represent its severity. Cardiologists frequently use these peptides as natriuretic and vasorelaxant agents to treat failing hearts. Recently, we identified the enhancer CR9 which induces ANP/BNP gene expressions during heart failure. In addition, we established in vivo live imaging system for heart failure by generating a transgenic mouse line in which CR9 enhancer and luciferase reporter gene are introduced into the germline.
The mechanism inducing the CR9 enhancer in failing hearts is still unknown. We are currently working on identification of transcription factors binding to CR9 as potential therapeutic targets which induce both ANP and BNP.

Heart is composed by various cellular populations, such as cardiomyocytes, fibroblasts, endothelial cells, resident immune cells, and so on. Understanding the transcriptome of each population and the network among them is essential for formulating precise therapeutic strategies to heart diseases. We are now working on the transcriptome analysis in each cellular population by flow cytometry and single-cell RNA sequencing of cells isolated from diseased hearts. Our goal is to reveal the transcriptome network among each population and to establish the screening system for identifying potential therapeutic targets in diseased hearts.