000285049 001__ 285049
000285049 005__ 20260209105308.0
000285049 0247_ $$2doi$$a10.1038/s41593-025-02123-w
000285049 0247_ $$2pmid$$apmid:41398476
000285049 0247_ $$2pmc$$apmc:PMC12880921
000285049 0247_ $$2ISSN$$a1097-6256
000285049 0247_ $$2ISSN$$a1546-1726
000285049 037__ $$aDZNE-2026-00173
000285049 041__ $$aEnglish
000285049 082__ $$a610
000285049 1001_ $$00009-0005-0034-0595$$aGonzález-Gallego, Judit$$b0
000285049 245__ $$aA fully iPS-cell-derived 3D model of the human blood-brain barrier for exploring neurovascular disease mechanisms and therapeutic interventions.
000285049 260__ $$aNew York, NY$$bNature America$$c2026
000285049 3367_ $$2DRIVER$$aarticle
000285049 3367_ $$2DataCite$$aOutput Types/Journal article
000285049 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1770630256_24273
000285049 3367_ $$2BibTeX$$aARTICLE
000285049 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000285049 3367_ $$00$$2EndNote$$aJournal Article
000285049 520__ $$aBlood-brain barrier (BBB) integrity is critical for brain homeostasis, with malfunctions contributing to neurovascular and neurodegenerative disorders. Mechanistic studies on BBB function have been mostly conducted in rodent and in vitro models, which recapitulate some disease features, but have limited translatability to humans and pose challenges for drug discovery. Here we report on a fully human induced pluripotent stem (iPS)-cell-derived, microfluidic three-dimensional (3D) BBB model consisting of endothelial cells (ECs), mural cells and astrocytes. Our model expresses typical fate markers, forms a barrier in vessel-like tubes and enables perfusion, including with human blood. Deletion of FOXF2 in ECs, a major risk gene for cerebral small vessel disease, induced key features of BBB dysfunction, including compromised cell junction integrity and enhanced caveolae formation. Proteomic analysis revealed dysregulated endocytosis and cell junction pathways. Disease features phenocopied those seen in mice with EC-specific Foxf2 deficiency. Moreover, lipid-nanoparticle-based treatment with Foxf2 mRNA rescued BBB deficits, demonstrating the potential for drug development.
000285049 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000285049 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x1
000285049 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x2
000285049 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000285049 650_7 $$2NLM Chemicals$$aForkhead Transcription Factors
000285049 650_2 $$2MeSH$$aBlood-Brain Barrier: physiology
000285049 650_2 $$2MeSH$$aHumans
000285049 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: physiology
000285049 650_2 $$2MeSH$$aAnimals
000285049 650_2 $$2MeSH$$aForkhead Transcription Factors: genetics
000285049 650_2 $$2MeSH$$aEndothelial Cells: physiology
000285049 650_2 $$2MeSH$$aMice
000285049 650_2 $$2MeSH$$aAstrocytes: physiology
000285049 650_2 $$2MeSH$$aCells, Cultured
000285049 7001_ $$00009-0007-8073-9524$$aTodorov-Völgyi, Katalin$$b1
000285049 7001_ $$0P:(DE-2719)2810938$$aMüller, Stephan A$$b2
000285049 7001_ $$aAntesberger, Sophie$$b3
000285049 7001_ $$00000-0002-8627-1260$$aTodorov, Mihail Ivilinov$$b4
000285049 7001_ $$aMalik, Rainer$$b5
000285049 7001_ $$aGrimalt-Mirada, Rita$$b6
000285049 7001_ $$aGonçalves, Carolina Cardoso$$b7
000285049 7001_ $$0P:(DE-2719)2812260$$aSchifferer, Martina$$b8
000285049 7001_ $$0P:(DE-2719)9000614$$aKislinger, Georg$$b9$$udzne
000285049 7001_ $$aWeisheit, Isabel$$b10
000285049 7001_ $$aLindner, Barbara$$b11
000285049 7001_ $$aCrusius, Dennis$$b12
000285049 7001_ $$aKroeger, Joseph$$b13
000285049 7001_ $$00000-0002-6432-1888$$aBorri, Mila$$b14
000285049 7001_ $$aErturk, Ali$$b15
000285049 7001_ $$aNelson, Mark$$b16
000285049 7001_ $$0P:(DE-2719)2810727$$aMisgeld, Thomas$$b17
000285049 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan F$$b18
000285049 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b19
000285049 7001_ $$0P:(DE-2719)2010112$$aPaquet, Dominik$$b20
000285049 773__ $$0PERI:(DE-600)1494955-6$$a10.1038/s41593-025-02123-w$$gVol. 29, no. 2, p. 479 - 492$$n2$$p479 - 492$$tNature neuroscience$$v29$$x1097-6256$$y2026
000285049 8564_ $$uhttps://pub.dzne.de/record/285049/files/DZNE-2026-00173.pdf$$yRestricted
000285049 8564_ $$uhttps://pub.dzne.de/record/285049/files/DZNE-2026-00173.pdf?subformat=pdfa$$xpdfa$$yRestricted
000285049 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810938$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000285049 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812260$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b8$$kDZNE
000285049 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)9000614$$aExternal Institute$$b9$$kExtern
000285049 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810727$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b17$$kDZNE
000285049 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2181459$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b18$$kDZNE
000285049 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000030$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b19$$kDZNE
000285049 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000285049 9131_ $$0G:(DE-HGF)POF4-351$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vBrain Function$$x1
000285049 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x2
000285049 915__ $$0StatID:(DE-HGF)0430$$2StatID$$aNational-Konsortium$$d2025-11-07$$wger
000285049 915__ $$0StatID:(DE-HGF)3003$$2StatID$$aDEAL Nature$$d2025-11-07$$wger
000285049 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNAT NEUROSCI : 2022$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2025-11-07
000285049 915__ $$0StatID:(DE-HGF)9925$$2StatID$$aIF >= 25$$bNAT NEUROSCI : 2022$$d2025-11-07
000285049 9201_ $$0I:(DE-2719)1110006$$kAG Lichtenthaler$$lNeuroproteomics$$x0
000285049 9201_ $$0I:(DE-2719)1110000-4$$kAG Misgeld$$lNeuronal Cell Biology$$x1
000285049 9201_ $$0I:(DE-2719)5000022$$kAG Dichgans$$lVascular Cognitive Impairment & Post-Stroke Dementia$$x2
000285049 980__ $$ajournal
000285049 980__ $$aEDITORS
000285049 980__ $$aVDBINPRINT
000285049 980__ $$aI:(DE-2719)1110006
000285049 980__ $$aI:(DE-2719)1110000-4
000285049 980__ $$aI:(DE-2719)5000022
000285049 980__ $$aUNRESTRICTED