Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood–brain barrier dysfunction module

Research output: Contribution to journalArticle

Authors

  • Roeben Nocon Munji
  • Allison Luen Soung
  • Geoffrey Aaron Weiner
  • Fabien Sohet
  • Bridgette Deanne Semple
  • Alpa Trivedi
  • Kayleen Gimlin
  • Masakazu Kotoda
  • Masaaki Korai
  • Sidar Aydin
  • Austin Batugal
  • Anne Christelle Cabangcala
  • Patrick Georg Schupp
  • Michael Clark Oldham
  • Tomoki Hashimoto
  • Linda J. Noble-Haeusslein
  • Richard Daneman

External Institution(s)

  • University of California at San Diego
  • University of California at San Francisco
  • St. Joseph's Hospital and Medical Center

Details

Original languageEnglish (US)
Pages (from-to)1892-1902
Number of pages11
JournalNature Neuroscience
Volume22
Issue number11
StatusPublished - Nov 1 2019
Peer-reviewedYes

Abstract

Blood vessels in the CNS form a specialized and critical structure, the blood–brain barrier (BBB). We present a resource to understand the molecular mechanisms that regulate BBB function in health and dysfunction during disease. Using endothelial cell enrichment and RNA sequencing, we analyzed the gene expression of endothelial cells in mice, comparing brain endothelial cells with peripheral endothelial cells. We also assessed the regulation of CNS endothelial gene expression in models of stroke, multiple sclerosis, traumatic brain injury and seizure, each having profound BBB disruption. We found that although each is caused by a distinct trigger, they exhibit strikingly similar endothelial gene expression changes during BBB disruption, comprising a core BBB dysfunction module that shifts the CNS endothelial cells into a peripheral endothelial cell-like state. The identification of a common pathway for BBB dysfunction suggests that targeting therapeutic agents to limit it may be effective across multiple neurological disorders.

Citation formats

APA

Munji, R. N., Soung, A. L., Weiner, G. A., Sohet, F., Semple, B. D., Trivedi, A., ... Daneman, R. (2019). Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood–brain barrier dysfunction module. Nature Neuroscience, 22(11), 1892-1902. https://doi.org/10.1038/s41593-019-0497-x

Harvard

Munji, RN, Soung, AL, Weiner, GA, Sohet, F, Semple, BD, Trivedi, A, Gimlin, K, Kotoda, M, Korai, M, Aydin, S, Batugal, A, Cabangcala, AC, Schupp, PG, Oldham, MC, Hashimoto, T, Noble-Haeusslein, LJ & Daneman, R 2019, 'Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood–brain barrier dysfunction module', Nature Neuroscience, vol. 22, no. 11, pp. 1892-1902. https://doi.org/10.1038/s41593-019-0497-x