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.

Multi-Omics Profiling of Human Endothelial Cells from the Coronary Artery and Internal Thoracic Artery Reveals Molecular but Not Functional Heterogeneity

“…Although molecular heterogeneity between different EC lineages [10][11][12][13][14][15] and ECs in distinct organs of the human body is well established [6][7][8][9], its pathophysiological and clinical significance remain unclear. CABG surgery, which is a seminal technique to treat coronary artery disease, employs the construction of an artificial bypass between the coronary artery and aorta (if using SV) or between the coronary artery and ITA (in the case of single or bilateral ITA grafting) and therefore links the coronary artery with a venous or arterial conduit, bringing their ECs into close proximity [24][25][26][27].…”

“…Rather than being a simple semi-permeable barrier protecting the blood vessels from thrombosis, lipid retention, and mineral deposition, endothelial cells (ECs) deploy numerous angiocrine factors including cytokines, growth factors, vasoactive substances, and other signaling molecules regulating vascular and systemic homeostasis in a juxtacrine or paracrine manner [1][2][3][4][5]. Single-cell RNA sequencing has demonstrated an organ-specific pattern of EC differentiation [6][7][8][9] and molecular heterogeneity between arterial, capillary, venous, and lymphatic ECs [10][11][12][13][14][15]. Recent advances in single-cell analysis and endothelial differentiation fostered a concept of therapeutic lymphangiogenesis, a treatment implying the guided regeneration of lymphatic networks upon the lymph node dissection to remove or ameliorate lymphoedema [16][17][18].…”

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 ).…”