Organ-Specific Endothelial Cell Differentiation and Impact of Microenvironmental Cues on Endothelial Heterogeneity

• Published in: International journal of molecular sciences Vol. 23; no. 3; p. 1477
• Main Authors: Gifre-Renom, Laia, Daems, Margo, Luttun, Aernout, Jones, Elizabeth A V
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.01.2022; MDPI
• Subjects: Angiogenesis; Animals; Biomechanics; Blood vessels; Brain research; Cardiomyocytes; Cell culture; Cell Differentiation; Cellular Microenvironment; Computer applications; Coronary vessels; Differentiation (biology); Embryos; endothelial cell; Endothelial cells; Endothelial Cells - metabolism; Endothelium; Endothelium, Vascular - metabolism; Epigenetics; Gene expression; Heart; Heterogeneity; Humans; microenvironment; Microenvironments; Microvasculature; Mimicry; Molecular biology; Organ Specificity; organ-specific signature; Organs; Permeability; Phenotypes; phenotypic drift; Proteomics; Review; Shear stress; Tissue Engineering; Transcriptomics; vascular development; Veins & arteries; mechanobiology; microenvironment; vascular development; endothelial cell; phenotypic drift; extracellular matrix; heterogeneity; organ-specific signature
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031477

Endothelial cells throughout the body are heterogeneous, and this is tightly linked to the specific functions of organs and tissues. Heterogeneity is already determined from development onwards and ranges from arterial/venous specification to microvascular fate determination in organ-specific differentiation. Acknowledging the different phenotypes of endothelial cells and the implications of this diversity is key for the development of more specialized tissue engineering and vascular repair approaches. However, although novel technologies in transcriptomics and proteomics are facilitating the unraveling of vascular bed-specific endothelial cell signatures, still much research is based on the use of insufficiently specialized endothelial cells. Endothelial cells are not only heterogeneous, but their specialized phenotypes are also dynamic and adapt to changes in their microenvironment. During the last decades, strong collaborations between molecular biology, mechanobiology, and computational disciplines have led to a better understanding of how endothelial cells are modulated by their mechanical and biochemical contexts. Yet, because of the use of insufficiently specialized endothelial cells, there is still a huge lack of knowledge in how tissue-specific biomechanical factors determine organ-specific phenotypes. With this review, we want to put the focus on how organ-specific endothelial cell signatures are determined from development onwards and conditioned by their microenvironments during adulthood. We discuss the latest research performed on endothelial cells, pointing out the important implications of mimicking tissue-specific biomechanical cues in culture.