Transcriptome studies of inherited dilated cardiomyopathies.

Abstract

Dilated cardiomyopathy (DCM) is a group of heart muscle diseases that often lead to heart failure, with more than 50 causative genes have being linked to DCM. The heterogenous nature of the inherited DCMs suggest the need of precision medicine. Consistent with this emerging concept, transcriptome studies in human patients with DCM indicated distinct molecular signature for DCMs of different genetic etiology. To facilitate this line of research, we reviewed the status of transcriptome studies of inherited DCMs by focusing on three predominant DCM causative genes, TTN, LMNA, and BAG3. Besides studies in human patients, we summarized transcriptomic analysis of these inherited DCMs in a variety of model systems ranging from iPSCs to rodents and zebrafish. We concluded that the RNA-seq technology is a powerful genomic tool that has already led to the discovery of new modifying genes, signaling pathways, and related therapeutic avenues. We also pointed out that both temporal (different pathological stages) and spatial (different cell types) information need to be considered for future transcriptome studies. While an important bottle neck is the low throughput in experimentally testing differentially expressed genes, new technologies in efficient animal models such as zebrafish starts to be developed. It is anticipated that the RNA-seq technology will continue to uncover both unique and common pathological events, aiding the development of precision medicine for inherited DCMs.