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 Dermadi, 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 and Eugene C. Butcher ()
Additional contact information
Kevin Brulois: Stanford University School of Medicine
Anusha Rajaraman: Stanford University School of Medicine
Agata Szade: Stanford University School of Medicine
Sofia Nordling: Stanford University School of Medicine
Ania Bogoslowski: Cumming School of Medicine, University of Calgary
Denis Dermadi: Stanford University School of Medicine
Milladur Rahman: Stanford University School of Medicine
Helena Kiefel: Stanford University School of Medicine
Edward O’Hara: Stanford University School of Medicine
Jasper J. Koning: Vrije Universiteit Medical Center
Hiroto Kawashima: Hoshi University
Bin Zhou: Chinese Academy of Sciences
Dietmar Vestweber: Max Planck Institute for Molecular Biomedicine
Kristy Red-Horse: Stanford University
Reina E. Mebius: Vrije Universiteit Medical Center
Ralf H. Adams: University of Münster, Faculty of Medicine
Paul Kubes: Cumming School of Medicine, University of Calgary
Junliang Pan: Stanford University School of Medicine
Eugene C. Butcher: Stanford University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17291-5

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