Spatially organized cellular communities inside of the human heart

The heart is a spectacular organ with a meticulous and straightforward structure, precise function and remarkable recovery mechanisms. Despite its apparent simplicity, we still struggle to understand the way of inter-cellular communication, the signal transduction through all the heart, the unitary reaction to external environment and the prompt correction of any deviation which can affect the functionality of the entire organ. 

In the paper published in Nature by Farah et al, novel techniques are combined to identify potential different population of ventricular cells. Using single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization (MERFISH) on developing human hearts, multiple subpopulations of ventricular cardiomyocyte subpopulation were identified, which displayed unexpected anatomical localization and interaction with other cells subpopulations, such as fibroblasts, endothelial and endocardial cells. 12 different cardiomyocytes subpopulation populate distinct anatomical regions in the heart and seems to exercise different functions. Novel subpopulations of cardiomyocytes were identified in the valve’s leaflets, atrium and atrioventricular node, exhibiting functional differences compared with all other cardiomyocyte subpopulations. Similar, different subpopulations of fibroblast, endocardial and neuronal cells were identified in atrium and ventricles. These types of cells communicate and signaling with cardiomyocytes, forming 13 distinct cardiac structures, called by the authors “cellular communities”, organized in laminar layers. Using an in vitro 3D bioprinted multilayer ventricular wall model, the authors identified the role of PLXN-SEMA signaling in structural ventricular organization, orchestrating and directing all cellular communities and allocating specific functions to the cardiomyocytes during the development of the human heart. 

This study demonstrates the complexity of the cardiac tissue, how distinct cell types specialize and organize into cardiac structures and how they interact with other cell types to maintain heart function. How these cell communities react and transform during pathological conditions remains to be investigated. Therefore, we must change our simplistic way to approach the heart pathology in order to be able to develop novel therapeutical strategies to treat cardiac diseases, to prevent ventricular remodeling and heart failure in affected patients.