Endothelial ontogeny and the establishment of vascular heterogeneity

Abstract

The establishment of distinct cellular identities was pivotal during the evolution of Metazoa, enabling the emergence of an array of specialized tissues with different functions. In most animals including vertebrates, cell specialization occurs in response to a combination of intrinsic (e.g., cellular ontogeny) and extrinsic (e.g., local environment) factors that drive the acquisition of unique characteristics at the single‐cell level. The first functional organ system to form in vertebrates is the cardiovascular system, which is lined by a network of endothelial cells whose organ‐specific characteristics have long been recognized. Recent genetic analyses at the single‐cell level have revealed that heterogeneity exists not only at the organ level but also between neighboring endothelial cells. Thus, how endothelial heterogeneity is established has become a key question in vascular biology. Drawing upon evidence from multiple organ systems, here we will discuss the role that lineage history may play in establishing endothelial heterogeneity.

Cardiac Lymphangiogenesis in CVDs

“…In embryos, after arteriovenous endothelial differentiation controlled by the NOTCH (neurogenic locus notch homolog protein) signal transduction pathway, the NR2F2/COUP-TFII (COUP transcription factor), SOX18 (SRY-related HMG-box), and PROX1 (prospero homeobox protein-1) transcription factors trigger the lymphatic differentiation program in venous vessels. 8 Genetic lineage-tracing and clonal analyses have demonstrated that cardiac lymphatic endothelial cells (LECs) on the ventral side of the cardiac ventricles originate also from nonvenous sources of the second heart field 9 and that tissue-resident macrophages are involved in the regulation of lymphatic vessel growth and patterning in the developing heart. 10 Experimental work has demonstrated that cardiac lymphangiogenesis is reactivated in CVDs, such as atherosclerosis and MI, as well as in pathological cardiac hypertrophy, resulting from pressure overload induced by Ang II (angiotensin II) or by surgical transaortic constriction.…”

Historical and current perspectives on blood endothelial cell heterogeneity in the brain

“…The initial steps of vascular development take place during gastrulation as mesodermal progenitors commit to an endothelial fate [ 85 , 86 ]. vECs have been shown to derive from both the lateral plate mesoderm and the paraxial mesoderm (also known as the presomitic mesoderm) in zebrafish [ 87 – 89 ], chicks [ 90 – 92 ], and mice [ 93 – 95 ].…”

Direct specification of lymphatic endothelium from non-venous angioblasts

“…1f ) 8,20 . Due to the restricted contribution of the Pax3 -lineage to LECs of the trunk 21 , at each stage we dissected embryos at the level of the otic vesicle and first pharyngeal arch ( Fig. 1f ).…”