Cardiac cell lineages that form the heart

Abstract

Myocardial cells ensure the contractility of the heart, which also depends on other mesodermal cell types for its function. Embryological experiments had identified the sources of cardiac precursor cells. With the advent of genetic engineering, novel tools have been used to reconstruct the lineage tree of cardiac cells that contribute to different parts of the heart, map the development of cardiac regions, and characterize their genetic signature. Such knowledge is of fundamental importance for our understanding of cardiogenesis and also for the diagnosis and treatment of heart malformations.

Figure 1.

Genetic signature of cardiac precursor cells. (A) Genetic origin of cardiac components, summarizing results from genetic tracing at the population level. (B) In vitro differentiation potential of cardiac precursors, summarizing results from clonal differentiation assays of ES cells or precardiac mesoderm, after cell sorting. (C) Schematic representation of Mesp1-positive cells leaving the primitive streak (PS) (E6.5) contributing to the heart fields (E7.5) and to the tissues of the mature heart (E14.5), with color coding as in A and B. AA, aortic arch arteries; Ao, aorta; CMs, cardiomyocytes; ECs, endothelial or endocardial cells; ICV, inferior caval vein; IVS, interventricular septum; LA, left atrium; LSCV, left superior caval vein; LV, left ventricle; OFT, outflow tract; PA, pulmonary arteries; PEO, proepicardial organ; PV, pulmonary vein; RA; right atrium; RSCV, right superior caval vein; RV, right ventricle; SCV, superior caval vein; SMs, smooth muscle cells.

Figure 2.

Regionalization of the heart. (A) First (red) and second (green) heart fields and anterior (pale green/yellow) or posterior (dark green) subdomains of the second heart field are shown at different stages of heart and head development. Regions of the heart with a dual origin are shown with colored dots. (B) Left (dark blue)/right (pale blue) derivatives of the second heart field, also showing right and left facial expression muscles in the head. Stages are as in A. ao, aorta; iAVC, inferior atrioventricular canal; sAVC, superior atrioventricular canal; E, embryonic day; LA, left atrium; dLA, dorsal left atrium; dLCA, dorsal left common atrium; vLCA, ventral left common atrium; LSCV, left superior caval vein; LV, left ventricle; OFT, outflow tract; PhA, pharyngeal arches; pt, pulmonary trunk; PV, pulmonary vein; RA, right atrium; RCA, right common atrium; RSCV, right superior caval vein; RV, right ventricle.

Figure 3.

Lineage tree of myocardial cells. A model of the lineage relationships between myocardial cells in different parts of the heart and skeletal muscles of the head is presented, summarizing results obtained in the mouse by retrospective clonal analysis. Progressive steps in lineage segregation are presented following the column on the right of the lineage tree. BA, branchial arch; iAVC, inferior atrioventricular canal; sAVC, superior atrioventricular canal; LA, left atrium; LSCV, left superior caval vein; LV, left ventricle; PV, pulmonary vein; RA, right atrium; RSCV, right superior caval vein; RV, right ventricle.