Abstract
Novel regenerative therapies may stem from deeper understanding of the mechanisms governing cardiovascular lineage diversification. Using enhancer mapping and live imaging in avian embryos, and genetic lineage tracing in mice, we investigated the spatio-temporal dynamics of cardiovascular progenitor populations. We show that expression of the cardiac transcription factor Nkx2.5 marks a mesodermal population outside of the cardiac crescent in the extraembryonic and lateral plate mesoderm, with characteristics of hemogenic angioblasts. Extra-cardiac Nkx2.5 lineage progenitors migrate into the embryo and contribute to clusters of CD41+/CD45+ and RUNX1+ cells in the endocardium, the aorta-gonad-mesonephros region of the dorsal aorta and liver. We also demonstrated that ectopic expression of Nkx2.5 in chick embryos activates the hemoangiogenic gene expression program. Taken together, we identified a hemogenic angioblast cell lineage characterized by transient Nkx2.5 expression that contributes to hemogenic endothelium and endocardium, suggesting a novel role for Nkx2.5 in hemoangiogenic lineage specification and diversification.
Highlights
Development of the cardiovascular system takes place during the early stages of embryogenesis
Cellular and molecular analyses indicate that a subset of extra-embryonic/lateral plate mesoderm (LPM)-derived hemogenic angioblasts travels via the inflow tract to populate the heart endocardium
Our results in both chick and mouse models demonstrate that the hemogenic endothelium in the DA and endocardium derives, at least in part, from Nkx2.5 lineage+ angioblast progenitors that may contribute to hematopoietic stem cells (HSCs) in the fetal liver (Figure 10)
Summary
Development of the cardiovascular system takes place during the early stages of embryogenesis. Cardiac progenitors residing in the cardiac crescent are formed from the first heart field (FHF) located in the anterior lateral plate mesoderm (LPM). Developmental Biology and Stem Cells eLife digest As an animal embryo develops, it establishes a circulatory system that includes the heart, vessels and blood. Vessels and blood initially form in the yolk sac, a membrane that surrounds the embryo. These yolk sac vessels act as a rudimentary circulatory system, connecting to the heart and blood vessels within the embryo itself. Cells in the inner layer of the largest blood vessel (known as the dorsal aorta) generate blood stem cells that give rise to the different types of blood cells
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