ArticleArteriosclerosis, thrombosis, and vascular biology2026
Generation of hiPSC-Derived Brain Microvascular Endothelial Cells Using Directed Differentiation and Transcriptional Reprogramming.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed.
- ETS-guided iPSC-endothelial models recapitulate malaria pathogenesis.EMBO molecular medicine · 2026Article
- Modulation of miR-23b Wnt/β-catenin Axis Strengthens Endothelial Barrier Properties.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- High prevalence of CNS-directed autoantibodies in patients with schizophrenia.bioRxiv : the preprint server for biology · 2026Article
- Human bone marrow-mesenchymal stem cells differentiation into brain-like endothelial cells.Turkish journal of biology = Turk biyoloji dergisi · 2026Article
- ApoE4 disrupts intracellular trafficking and iron homeostasis in a reproducible iPSC-based model of human brain endothelial cells.Stem cell reports · 2025Article
- Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model.Nature communications · 2025Article
- Generating iAstrocytes From Human Induced Pluripotent Stem Cells by Combining Low-Density Passaging of Neural Progenitor Cells and Transcription Factor NFIA Transdifferentiation.Current protocols · 2024Article
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8 authors.
Funding
Abstract
backgroundModeling the human blood-brain barrier (BBB) is limited by the lack of robust protocols to generate induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs). Current methods generate cells that do not fully recapitulate key BMEC functions or the brain endothelial transcriptome identity.
methodsTo address this gap, we combined directed differentiation of human iPSCs into BBB-primed endothelial cells with overexpression of FOXF2 (forkhead box F2) and ZIC3 (zic family zinc finger 3), transcription factors critical for BMEC identity, to generate reprogrammed BMECs (rBMECs) from 3 iPSC lines. We performed immunofluorescence, functional analyses, and bulk RNA sequencing to characterize these cells. We cocultured rBMECs with iPSC-derived astrocytes and pericytes in the MIMETAS microfluidics platform to assess how 3-dimensional culture influences their BBB properties. Finally, we generated rBMECs expressing familial Alzheimer disease mutation
resultsTranscriptomic and functional analyses show that rBMECs express a subset of the BBB transcriptome and exhibit stronger paracellular barrier properties, lower caveolar-mediated transport, and comparable PGP (P-glycoprotein) activity compared with primary human BMECs. rBMECs interact with human iPSC-derived pericytes and astrocytes to form a 3D neurovascular system in the MIMETAS microfluidics platform with robust BBB properties. Finally,
conclusionsThis protocol generates rBMECs with strong BBB properties and a brain-specific transcriptome signature. In addition, the iPSC-derived 3D neurovascular unit system shows some similar properties to the in vivo human BBB. Finally, familial Alzheimer disease mutation
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