Endocardial-Myocardial Interactions During Early Cardiac Differentiation and Trabeculation

Abstract

Throughout the continuum of heart formation, myocardial growth and differentiation occurs in concert with the development of a specialized population of endothelial cells lining the cardiac lumen, the endocardium. Once the endocardial cells are specified, they are in close juxtaposition to the cardiomyocytes, which facilitates communication between the two cell types that has been proven to be critical for both early cardiac development and later myocardial function. Endocardial cues orchestrate cardiomyocyte proliferation, survival, and organization. Additionally, the endocardium enables oxygenated blood to reach the cardiomyocytes. Cardiomyocytes, in turn, secrete factors that promote endocardial growth and function. As misregulation of this delicate and complex endocardial-myocardial interplay can result in congenital heart defects, further delineation of underlying genetic and molecular factors involved in cardiac paracrine signaling will be vital in the development of therapies to promote cardiac homeostasis and regeneration. Herein, we highlight the latest research that has advanced the elucidation of endocardial-myocardial interactions in early cardiac morphogenesis, including endocardial and myocardial crosstalk necessary for cellular differentiation and tissue remodeling during trabeculation, as well as signaling critical for endocardial growth during trabeculation.

Tissue-embedded stretchable nanoelectronics reveal endothelial cell–mediated electrical maturation of human 3D cardiac microtissues

“…CM/EC coculture has previously been shown to be mutually beneficial to both cell types (4)(5)(6)(7)(8)(9)(10)(11)(12), and, in this study, we sought to understand how hiPSC-ECs can accelerate electrical maturation of hiPSC-CMs. ECs and CMs participate in cross-talk via paracrine signaling as well as direct cell-to-cell contact (78).…”

“…Communication between endothelial cells (ECs) and CMs is important during development ( 4 , 5 ). For example, neuregulin (NRG) is secreted by ECs during early development to direct CM phenotype away from a nodal subtype ( 6 ) and promote cardiac trabeculation via ErbB receptor signaling ( 7 ).…”

Heart-on-a-chip systems: disease modeling and drug screening applications

“…Given that CMs comprise only 30% by number of total cells in the heart, co-culture with other cell types, such as fibroblasts, neural cells, endothelial cells, and immune cells has been shown to promote maturation through intercellular interaction and paracrine signaling. 8,[212][213][214][215][216][217][218][219][220][221][222][223][224][225][226] Co-culture of hESC-CMs with human cardiac fibroblasts (at an optimized 4 : 1 ratio) in a microfluidic chip containing an array of microposts was found to improve tissue maturity and anisotropy after just 2 weeks (Fig. 3c).…”

Functions of cilia in cardiac development and disease

“…The presence of cardiac trabeculae increases cardiac output and facilitates nutrient and oxygen exchange in the embryonic myocardium prior to the establishment of the coronary vasculature. After the establishment of coronary vasculature, the trabeculae undergo extensive remodeling and coalesce together with the cardiac wall to form a thick muscular layer (Lai et al, 2010;Qu et al, 2022;Samsa et al, 2013Samsa et al, , 2015M. Wu, 2018;Figure 2e).…”