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. 2024 Oct 21;59(20):2687-2703.e6.
doi: 10.1016/j.devcel.2024.06.015. Epub 2024 Jul 17.

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

Yiyun Wang  1 , Neelima Thottappillil  1 , Mario Gomez-Salazar  1 , Robert J Tower  2 , Qizhi Qin  1 , Ishbel Camila Del Rosario Alvia  1 , Mingxin Xu  1 , Masnsen Cherief  1 , Ray Cheng  1 , Mary Archer  1 , Shreya Arondekar  1 , Sashank Reddy  3 , Kristen Broderick  3 , Bruno Péault  4 , Aaron W James  5
Affiliations

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

Yiyun Wang et al. Dev Cell. .

Abstract

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, CD201Low expression typified a mesodermal committed subset with higher osteogenesis and less proliferation than CD201High cells, with a downstream effect on canonical Wnt signaling through DACT2. CD201Low cells also displayed high translational potential for bone tissue generation.

Keywords: blood vessel; mesenchymal stem/progenitor cells; ossicle formation; perivascular; spatial transcriptomics; stem cell niche; tunica adventitia.

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Conflict of interest statement

Declaration of interests A.W.J. declared scientific advisory board for Novadip LLC, consultant for Lifesprout LLC and Novadip LLC, and Editorial Board of Stem Cells, Bone Research, and American Journal of Pathology. K.B. declared consultant for Dilon Technologies. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies.

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