Parenchymal cues define Vegfa-driven venous angiogenesis by activating a sprouting competent venous endothelial subtype

Laetitia Préau, Anna Lischke, Melanie Merkel, Neslihan Oegel, Maria Weissenbruch, Andria Michael, Hongryeol Park, Dietmar Gradl, Christian Kupatt and Ferdinand Noble ()
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Laetitia Préau: Karlsruhe Institute of Technology (KIT)
Anna Lischke: Karlsruhe Institute of Technology (KIT)
Melanie Merkel: Karlsruhe Institute of Technology (KIT)
Neslihan Oegel: Karlsruhe Institute of Technology (KIT)
Maria Weissenbruch: Karlsruhe Institute of Technology (KIT)
Andria Michael: Karlsruhe Institute of Technology (KIT)
Hongryeol Park: Max Planck Institute for Molecular Biomedicine
Dietmar Gradl: Karlsruhe Institute of Technology (KIT)
Christian Kupatt: Technical University Munich, and DZHK (German Center for Cardiovascular Research), partner site Munich
Ferdinand Noble: Karlsruhe Institute of Technology (KIT)

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract Formation of organo-typical vascular networks requires cross-talk between differentiating parenchymal cells and developing blood vessels. Here we identify a Vegfa driven venous sprouting process involving parenchymal to vein cross-talk regulating venous endothelial Vegfa signaling strength and subsequent formation of a specialized angiogenic cell, prefabricated with an intact lumen and pericyte coverage, termed L-Tip cell. L-Tip cell selection in the venous domain requires genetic interaction between vascular Aplnra and Kdrl in a subset of venous endothelial cells and exposure to parenchymal derived Vegfa and Apelin. Parenchymal Esm1 controls the spatial positioning of venous sprouting by fine-tuning local Vegfa availability. These findings may provide a conceptual framework for understanding how Vegfa generates organo-typical vascular networks based on the selection of competent endothelial cells, induced via spatio-temporal control of endothelial Kdrl signaling strength involving multiple parenchymal derived cues generated in a tissue dependent metabolic context.

Date: 2024
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DOI: 10.1038/s41467-024-47434-x

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