Direct specification of lymphatic endothelium from mesenchymal progenitors.

During embryogenesis, endothelial cells (ECs) are generally described to arise from a common pool of progenitors termed angioblasts, which diversify through iterative steps of differentiation to form functionally distinct subtypes of ECs. A key example is the formation of lymphatic ECs (LECs), which are thought to arise largely through transdifferentiation from venous endothelium. Opposing this model, here we show that the initial expansion of mammalian LECs is primarily driven by the in situ differentiation of mesenchymal progenitors and does not require transition through an intermediate venous state.

Analysis of epicardial genes in embryonic mouse hearts with flow cytometry.

Genetic markers used to define discrete cell populations are seldom expressed exclusively in the population of interest and are, thus, unsuitable when evaluated individually, especially in the absence of spatial and morphological information. Here, we present fluorescence hybridization for flow cytometry to allow simultaneous analysis of multiple marker genes at the single whole-cell level, exemplified by application to the embryonic epicardium. The protocol facilitates multiplexed quantification of gene and protein expression and temporal changes across specific cell populations.

Coronary vessel formation in development and disease: mechanisms and insights for therapy.

The formation of new blood vessels after myocardial infarction (MI) is essential for the survival of existing and regenerated cardiac tissue. However, the extent of endogenous revascularization after MI is insufficient, and MI can often result in ventricular remodelling, progression to heart failure and premature death. The neutral results of numerous clinical trials that have evaluated the efficacy of angiogenic therapy to revascularize the infarcted heart reflect our poor understanding of the processes required to form a functional coronary vasculature.

Spatiotemporal Analysis Reveals Overlap of Key Proepicardial Markers in the Developing Murine Heart.

The embryonic epicardium, originating from the proepicardial organ (PEO), provides a source of multipotent progenitors for cardiac lineages, including pericytes, fibroblasts, and vascular smooth muscle cells. Maximizing the regenerative capacity of the adult epicardium depends on recapitulating embryonic cell fates. The potential of the epicardium to contribute coronary endothelium is unclear, due to conflicting Cre-based lineage trace data.

Non-muscle myosin IIB (Myh10) is required for epicardial function and coronary vessel formation during mammalian development.

The coronary vasculature is an essential vessel network providing the blood supply to the heart. Disruptions in coronary blood flow contribute to cardiac disease, a major cause of premature death worldwide. The generation of treatments for cardiovascular disease will be aided by a deeper understanding of the developmental processes that underpin coronary vessel formation.