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Wnt signaling mediates acquisition of blood-brain barrier properties in naïve endothelium derived from human pluripotent stem cells.

Authors
  • Gastfriend, Benjamin D1
  • Nishihara, Hideaki2
  • Canfield, Scott G1
  • Foreman, Koji L1
  • Englehardt, Britta2
  • Palecek, Sean P3
  • Shusta, Eric V3
  • 1 Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, United States. , (United States)
  • 2 University of Bern, Bern, Switzerland. , (Switzerland)
  • 3 Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, United States. , (United States)
Type
Published Article
Journal
eLife
Publisher
"eLife Sciences Organisation, Ltd."
Publication Date
Nov 10, 2021
Volume
10
Identifiers
DOI: 10.7554/eLife.70992
PMID: 34755601
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Endothelial cells (ECs) in the central nervous system (CNS) acquire their specialized blood-brain barrier (BBB) properties in response to extrinsic signals, with Wnt/β-catenin signaling coordinating multiple aspects of this process. Our knowledge of CNS EC development has been advanced largely by animal models, and human pluripotent stem cells (hPSCs) offer the opportunity to examine BBB development in an in vitro human system. Here we show that activation of Wnt signaling in hPSC-derived naïve endothelial progenitors, but not in matured ECs, leads to robust acquisition of canonical BBB phenotypes including expression of GLUT-1, increased claudin-5, decreased PLVAP and decreased permeability. RNA-seq revealed a transcriptome profile resembling ECs with CNS-like characteristics, including Wnt-upregulated expression of LEF1, APCDD1, and ZIC3. Together, our work defines effects of Wnt activation in naïve ECs and establishes an improved hPSC-based model for interrogation of CNS barriergenesis. © 2021, Gastfriend et al.

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