A molecular map of murine lymph node blood vascular endothelium at single cell resolution
Kevin Brulois, Anusha Rajaraman, Agata Szade, Sofia Nordling, Ania Bogoslowski, Denis Đermadi, Milladur Rahman, Helena Kiefel, Edward O’Hara, Jasper J. Koning, Hiroto Kawashima, Bin Zhou, Dietmar Vestweber, Kristy Red-Horse, Reina E. Mebius, Ralf H. Adams, Paul Kubes, Junliang Pan, Eugene C. Butcher
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 medullary venous population whose gene signature predicts a selective role in myeloid cell (vs lymphocyte) recruitment to the medulla, confirmed by videomicroscopy. We define five capillary subsets, including a capillary resident precursor (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 venous and arterial populations. Our single cell atlas provides a molecular roadmap of the lymph node blood vasculature and defines subset specialization for leukocyte recruitment and vascular homeostasis.