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Alk1 acts in non-endothelial VE-cadherin+ perineurial cells to maintain nerve branching during hair homeostasis

Author

Listed:
  • Gopal Chovatiya

    (Cornell University)

  • Kefei Nina Li

    (Cornell University)

  • Jonathan Li

    (Cornell University)

  • Sangeeta Ghuwalewala

    (Cornell University)

  • Tudorita Tumbar

    (Cornell University)

Abstract

Vascular endothelial (VE)-cadherin is a well-recognized endothelial cell marker. One of its interacting partners, the TGF-β receptor Alk1, is essential in endothelial cells for adult skin vasculature remodeling during hair homeostasis. Using single-cell transcriptomics, lineage tracing and gene targeting in mice, we characterize the cellular and molecular dynamics of skin VE-cadherin+ cells during hair homeostasis. We describe dynamic changes of VE-cadherin+ endothelial cells specific to blood and lymphatic vessels and uncover an atypical VE-cadherin+ cell population. The latter is not a predicted adult endovascular progenitor, but rather a non-endothelial mesenchymal perineurial cell type, which forms nerve encapsulating tubular structures that undergo remodeling during hair homeostasis. Alk1 acts in the VE-cadherin+ perineurial cells to maintain proper homeostatic nerve branching by enforcing basement membrane and extracellular matrix molecular signatures. Our work implicates the VE-cadherin/Alk1 duo, classically known as endothelial-vascular specific, in perineurial-nerve homeostasis. This has broad implications in vascular and nerve disease.

Suggested Citation

  • Gopal Chovatiya & Kefei Nina Li & Jonathan Li & Sangeeta Ghuwalewala & Tudorita Tumbar, 2023. "Alk1 acts in non-endothelial VE-cadherin+ perineurial cells to maintain nerve branching during hair homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40761-5
    DOI: 10.1038/s41467-023-40761-5
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    1. 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 & , 2020. "A molecular map of murine lymph node blood vascular endothelium at single cell resolution," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    2. Fabrizio Orsenigo & Costanza Giampietro & Aldo Ferrari & Monica Corada & Ariane Galaup & Sara Sigismund & Giuseppe Ristagno & Luigi Maddaluno & Gou Young Koh & Davide Franco & Vartan Kurtcuoglu & Dimo, 2012. "Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo," Nature Communications, Nature, vol. 3(1), pages 1-15, January.
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