Endothelial cell plasticity at the single-cell level

The vascular endothelium is characterized by a remarkable level of plasticity, which is the driving force not only of physiological repair/remodeling of adult tissues but also of pathological angiogenesis. The resulting heterogeneity of endothelial cells (ECs) makes targeting the endothelium challenging, no less because many EC phenotypes are yet to be identified and functionally inventorized. Efforts to map the vasculature at the single-cell level have been instrumental to capture the diversity of EC types and states at a remarkable depth in both normal and pathological states. Here, we discuss new EC subtypes and functions emerging from recent single-cell studies in health and disease. Interestingly, such studies revealed distinct metabolic gene signatures in different EC phenotypes, which deserve further consideration for therapy. We highlight how this metabolic targeting strategy could potentially be used to promote (for tissue repair) or block (in tumor) angiogenesis in a tissue or even vascular bed-specific manner.

Automated summary

The plasticity of vascular endothelial cells drives physiological repair and pathological angiogenesis, posing challenges for targeted therapy due to their heterogeneity and unidentified phenotypes. Single-cell studies have revealed the diversity of EC types and states, offering insights into new subtypes and functions in health and disease. Metabolic gene signatures in different EC phenotypes may hold therapeutic potential for promoting tissue repair or inhibiting tumor angiogenesis in a tissue-specific manner.