Multi-Omics Characterization of a Human Stem Cell-Based Model of Cardiac Hypertrophy

Life

Christian X. Andersson¹  Anders Jeppsson²  Sepideh Heydarkhan-Hagvall³  Peter Sartipy³  Markus Johansson³  Benjamin Ulfenborg³  Jane Synnergren³ 

[1]BioPharmaceuticals R&D Cell Therapy, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, SE-413 83 Gothenburg, Sweden

[2]Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden

[3]Systems Biology Research Center, School of Bioscience, University of Skövde, SE-541 28 Skövde, Sweden

关键词: cardiac hypertrophy;    cardiomyocytes;    disease model;    endothelin-1;    stem cells;    transcriptomics;   

DOI  :  10.3390/life12020293

来源: DOAJ

【 摘 要 】

Cardiac hypertrophy is an important and independent risk factor for the development of cardiac myopathy that may lead to heart failure. The mechanisms underlying the development of cardiac hypertrophy are yet not well understood. To increase the knowledge about mechanisms and regulatory pathways involved in the progression of cardiac hypertrophy, we have developed a human induced pluripotent stem cell (hiPSC)-based in vitro model of cardiac hypertrophy and performed extensive characterization using a multi-omics approach. In a series of experiments, hiPSC-derived cardiomyocytes were stimulated with Endothelin-1 for 8, 24, 48, and 72 h, and their transcriptome and secreted proteome were analyzed. The transcriptomic data show many enriched canonical pathways related to cardiac hypertrophy already at the earliest time point, e.g., cardiac hypertrophy signaling. An integrated transcriptome–secretome analysis enabled the identification of multimodal biomarkers that may prove highly relevant for monitoring early cardiac hypertrophy progression. Taken together, the results from this study demonstrate that our in vitro model displays a hypertrophic response on both transcriptomic- and secreted-proteomic levels. The results also shed novel insights into the underlying mechanisms of cardiac hypertrophy, and novel putative early cardiac hypertrophy biomarkers have been identified that warrant further investigation to assess their potential clinical relevance.

【 授权许可】

Unknown