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<p>Our understanding of how the body communicates with the brain to coordinate their functions is remarkably limited. At the blood-brain barrier (BBB), brain endothelial cells (BECs) are ideally positioned to mediate signaling between blood and brain parenchyma via direct communication with astrocyte perivascular processes (endfeet). We develop a method to define the mouse in vivo astrocyte endfoot proteome, which in combination with BEC-specific RNA-seq, reveal BEC to astrocyte endfoot ligand-receptor pairs that are modulated when mice are exposed to a peripheral inflammatory insult with lipopolysaccharide. We show that over 80% of these mouse BEC-endfoot ligand-receptor pairs are also found in the human BBB, with a subset of them differentially expressed in human multiple sclerosis or Alzheimer’s disease compared to healthy individuals. Our findings reveal dynamic BEC-endfoot communication pathways that are relevant to human physiology and provide methodology and datasets for the translational study of BEC-astrocyte crosstalk in health and disease.</p>

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Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月6日

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  • Steven A. Hill,
  • Isabel Bravo-Ferrer,
  • Austėja Čiulkinytė,
  • Noelia Pérez Ramos,
  • Ilaria Rossetti,
  • Chiara Colvin,
  • Paula Beltran-Lobo,
  • Carlos Parra-Pérez,
  • Katie Emelianova,
  • Owen Dando,
  • Beth Geary,
  • Raja S. Nirujogi,
  • Dario R. Alessi,
  • Do-Young Lee,
  • Youn-Bok Lee,
  • Blanca Díaz Castro

摘要

Our understanding of how the body communicates with the brain to coordinate their functions is remarkably limited. At the blood-brain barrier (BBB), brain endothelial cells (BECs) are ideally positioned to mediate signaling between blood and brain parenchyma via direct communication with astrocyte perivascular processes (endfeet). We develop a method to define the mouse in vivo astrocyte endfoot proteome, which in combination with BEC-specific RNA-seq, reveal BEC to astrocyte endfoot ligand-receptor pairs that are modulated when mice are exposed to a peripheral inflammatory insult with lipopolysaccharide. We show that over 80% of these mouse BEC-endfoot ligand-receptor pairs are also found in the human BBB, with a subset of them differentially expressed in human multiple sclerosis or Alzheimer’s disease compared to healthy individuals. Our findings reveal dynamic BEC-endfoot communication pathways that are relevant to human physiology and provide methodology and datasets for the translational study of BEC-astrocyte crosstalk in health and disease.