Single cell trajectories reveal a developmental sequence from angiogenic capillary progenitors to mature high endothelial cells

Abstract

Blood vascular endothelial cells (BECs) control the immune response by regulating blood flow and immune cell recruitment in lymphoid tissues. However, the diversity of BEC and their origins during immune angiogenesis remain unclear. Here we profile transcriptomes of BEC from peripheral lymph nodes and map phenotypes to the vasculature. We identify multiple subsets including a capillary resident progenitor (CRP) that displays stem cell and migratory gene signatures and contributes to homeostatic BEC turnover and to neogenesis of high endothelium after immunization. Cell alignments show retention of developmental programs along trajectories from CRP to mature HEC and arterial populations. Integrated analysis of mouse and human datasets reveals conserved cellular subsets and shared and divergent gene expression programs with implications for species differences in immune trafficking mechanisms. Our analyses provides a molecular roadmap of the lymph node blood vasculature and defines subset specialization for leukocyte recruitment and vascular homeostasis.