Abstract
Byline: Miguel G Rojas, Surgery, Univ of Miami, FL; Laisel Martinez, UNIVERSITY OF MIAMI, Miami, FL; Simone Pereira-Simon, Univ of Miami, Miami, FL; Zachary Zigmond, Univ of Miami, Miami, FL; Nieves Santos Falcon, Univ of Miami, Miami, FL; Alghidak Salama, Surgery, Univ of Miami, FL; Roberto I Vazquez-Padron, UNIVERSITY OF MIAMI, Miami, FL Introduction: The cells in veins that contribute to vascular disease have not been fully characterized. This study generated a cellular atlas of the human basilic vein that will help understand vein physiology and pathologies. Methods: Single-cell sequencing of four basilic veins from healthy organ donors. Results: The integrated single-cell profile of 15,747 vein cells revealed 13 populations containing canonical and non-canonical vascular markers. The SMC population represented 16% of cells, of which 8% were purely contractile and the remaining 8% had a modulated phenotype. One cluster of modulated SMCs expressed ECM genes (collagen type IV, FN1, and TNC) while retaining high expression of contractile markers (DES, MYH11, ©ÀACTG2). The other SMC cluster had unique expression of CD36, APOE, LPL, and STEAP4, characteristic of lipid-processing cells. Surprisingly, these non-diseased veins contained a high number of resident immune cells, including pro-inflammatory macrophages (9%), CD163- and HMOX1-expressing Mhem-like macrophages (18%), lymphocytes (5%), and small counts of neutrophils (0.3%) and mast cells (0.7%). The adventitial cell populations highlighted the fundamental role of this layer in vascular maintenance, remodeling, and angiogenesis. We found a significant number of vasa vasorum ECs (6.5%) which differentiated from the luminal subpopulation (3.5%) by CD34, KDR, NOTCH4, and ICAM2 expression. There were also two types of fibroblasts. Classical fibroblasts (19%) had high expression of collagen genes, while adipogenic fibroblasts (21%) were characterized by high levels of ECM-interacting fibulins, adipocyte-associated genes (ADH1B, APOD, CXCL14, IGF1), and modulators of angiogenesis (ADM and EFEMP1). CellCall analyses identified 46 overrepresented ligand-receptor communication pathways in all clusters, including CXCL, FGF, IL-6, and complement signaling. Communication between pro-inflammatory macrophages and luminal ECs was the most overrepresented signaling connection. Conclusions: This comprehensive atlas of the human vein will help identify cell subpopulations relevant to venous pathologies, without relying on extrapolations from arterial biology and focusing instead on the uniqueness of vein tissues.