A molecular map of lymph node blood vascular endothelium at single cell resolution

Abstract

Blood vascular endothelial cells (BECs) control the immune response by regulating immune cell recruitment, metabolite exchange and blood flow in lymphoid tissues. However, the diversity of BEC and their origins during immune angiogenesis remain poorly understood. Here we profile transcriptomes of BEC from mouse peripheral lymph nodes and map key phenotypes to the vasculature. Our analysis identifies multiple novel subsets including a venous population whose gene signature predicts an unexpectedly selective role in myeloid cell (vs lymphocyte) recruitment to the medulla, confirmed by 2 photon videomicroscopy. We define five phenotypes of capillary lining BEC including a capillary resident regenerative population (CRP) that displays stem cell and migratory gene signatures and contributes to homeostatic BEC turnover and to vascular neogenesis after immunization. Trajectory analyses reveal retention of developmental programs along a progression of cellular phenotypes from CRP to mature venous and arterial BEC subsets. Overall, our single cell atlas provides a molecular blueprint of the lymph node blood vasculature and defines subset specialization for immune cell recruitment and vascular homeostasis.