Spatial and temporal ECM expression pattern during human cardiogenesis ‐ learning from nature's blueprint

Abstract

During fetal cardiac development, extracellular matrix (ECM) compounds are recognized to be essential for cell differentiation and maturation processes. Thus, we aimed to identify spatial and temporal ECM expression pattern during human fetal cardiogenesis, in order to learn from these developmental cues for applictions in regenerative medicine. Therefore, we analyzed the temporal expression and the localization of six essential ECM molecules: collagen type I, III, IV and VI (COLI, COLIII, COLIV, COLVI), fibronectin (FN) and elastin (ELN). Here, we used human ventricular heart muscle tissues of different age groups: fetal first (week 4–12) and second (week 14–17) trimester, children (3–9 years), adults (50–70 years). We performed quantitative gene expression analysis of COL I, COL III, COL IV, COL VI, FN and ELN and analyzed temporal and spatial protein expression by immunofluorescence staining. We revealed a spatiotemporal distinct expression of collagen type IV during human cardiac development. Collagen type IV was highly expressed at the early onset of cardiogenesis, decreased during second trimester, where it was primarily detected in the epicardium, and increased postnatal around mature cardiomyocytes and in the epicardium. Collagen type I expression was the highest in first trimester ventricles and decreased during development. Here, we identified distinct spatiotemporal expression patterns of ECM proteins, which will serve as a blueprint for biomaterials that can be used for myocardial regeneration.