Search

During development, endothelial cells (ECs) undergo an extraordinary specialization by which generic capillary microcirculatory networks spanning from arteries to veins transform into patterned organotypic zonated blood vessels. These capillary ECs become specialized to support the cellular and metabolic demands of each specific organ, including supplying tissue-specific angiocrine factors that orchestrate organ development, maintenance of organ-specific functions and regeneration of injured adult organs. Here, we illustrate the mechanisms by which microenvironmental signals emanating from non-vascular niche cells induce generic ECs to acquire specific inter-organ and intra-organ functional attributes. We describe how perivascular, parenchymal and immune cells dictate vascular heterogeneity and capillary zonation, and how this system is maintained through tissue-specific signalling activated by vasculogenic and angiogenic factors and deposition of matrix components. We also discuss how perturbation of organotypic vascular niche cues lead to erasure of EC signatures, contributing to the pathogenesis of disease processes. We also describe approaches that use reconstitution of tissue-specific signatures of ECs to promote regeneration of damaged organs., Competing Interests: Competing interests: S.R. is an unpaid consultant for Angiocrine Bioscience., (© 2025. Springer Nature Limited.)

Atherosclerosis is a pervasive contributor to ischemic heart disease and stroke. Despite the advance of lipid-lowering therapies and anti-hypertensive agents, the residual risk of an atherosclerotic event remains high, and developing therapeutic strategies has proven challenging. This is due to the complexity of atherosclerosis with a spatial interplay of multiple cell types within the vascular wall. In this study, we generated an integrative high-resolution map of human atherosclerotic plaques combining single-cell RNA sequencing from multiple studies and spatial transcriptomics data from 12 human specimens with different stages of atherosclerosis. Here we show cell-type-specific and atherosclerosis-specific expression changes and spatially constrained alterations in cell-cell communication. We highlight the possible recruitment of lymphocytes via ACKR1 endothelial cells of the vasa vasorum, the migration of vascular smooth muscle cells toward the lumen by transforming into fibromyocytes and cell-cell communication in the plaque region, indicating an intricate cellular interplay within the adventitia and the subendothelial space in human atherosclerosis., Competing Interests: Competing interests: M.N., H.H., C.P., M.B., S.B. and V.D. are employed by Novo Nordisk A/S, which generated the spatial transcriptomics data. They hold minor stock portions as part of an employee offering program. S.H. is a co-founder and shareholder of Sequantrix GmbH and has research funding from AskBio. R.K. is a founder, shareholder and board member of Sequantrix GmbH; is a member of the scientific advisory board of Hybridize Therapeutics; has received honoraria for advisory boards and talks from Bayer, Chugai, Pfizer, Roche, Genentech, Eli Lilly and GlaxoSmithKline; and has research funding from Travere Therapeutics, Galapagos, Novo Nordisk and AskBio. All other authors indicated that no competing interests exist., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Brain vasculature formation begins with vessel invasion from the perineural vascular plexus, which expands through vessel sprouting and growth. Recent studies have indicated the existence of oligodendrocyte-vascular crosstalk during development. However, the relationship between oligodendrocyte progenitor cells (OPCs) and the ordered spatiotemporal vascularization of the neocortex has not been elucidated. Our findings suggest that OPCs play a complex role in the vessel density of the embryonic and postnatal neocortex. Analyses of normal human and mouse embryonic cerebral cortex show that vascularization and OPC distribution are tightly controlled in a spatially and temporally restricted manner, exhibiting a positive correlation. Loss of OPCs at both embryonic and postnatal stages led to a reduction in vascular density, suggesting that OPC populations play a role in vascular density. Nonetheless, dynamic observation on cultured brain slices and staining of tissue sections indicate that OPC migration is unassociated with the proximity to blood vessels, primarily occurring along radial glial cell processes. Additionally, in vitro experiments demonstrate that OPC secretions promote vascular endothelial cell (VEC) growth. Together, these observations suggest that vessel density is influenced by OPC secretions., (© 2024 Wiley Periodicals LLC.)