Integrated transcriptomics of human blood vessels defines a spatially controlled niche for early mesenchymal progenitor cells

Human blood vessel walls show concentric layers, with the outermost tunica adventitia harboring mesenchymal progenitor cells. These progenitor cells maintain vessel homeostasis and provide a robust cell source for cell-based therapies. However, human adventitial stem cell niche has not been studied in detail. Here, using spatial and single-cell transcriptomics, we characterized the phenotype, potential, and microanatomic distribution of human perivascular progenitors. Initially, spatial transcriptomics identified heterogeneity between perivascular layers of arteries and veins and delineated the tunica adventitia into inner and outer layers. From this spatial atlas, we inferred a hierarchy of mesenchymal progenitors dictated by a more primitive cell with a high surface expression of CD201 (PROCR). When isolated from humans and mice, CD201^Low expression typified a mesodermal committed subset with higher osteogenesis and less proliferation than CD201^High cells, with a downstream effect on canonical Wnt signaling through DACT2. CD201^Low cells also displayed high translational potential for bone tissue generation.