Schizophrenia-derived hiPSC brain microvascular endothelial-like cells show impairments in angiogenesis and blood–brain barrier function

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dc.contributor.authorCasas, Bárbara
dc.contributor.authorVitória, Gabriela
dc.contributor.authorPrieto, Catalina
dc.contributor.authorCasas, Mariana
dc.contributor.authorChacón, Carlos
dc.contributor.authorUhrig, Markus
dc.contributor.authorEzquer, Fernando
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorRehen, Stevens
dc.contributor.authorPalma, Verónica
dc.date.accessioned2022-11-14T18:28:20Z
dc.date.available2022-11-14T18:28:20Z
dc.date.issued2022
dc.description.abstractSchizophrenia (SZ) is a complex neuropsychiatric disorder, affecting 1% of the world population. Long-standing clinical observations and molecular data have pointed to a possible vascular deficiency that could be acting synergistically with neuronal dysfunction in SZ. As SZ is a neurodevelopmental disease, the use of human-induced pluripotent stem cells (hiPSC) allows disease biology modeling while retaining the patient’s unique genetic signature. Previously, we reported a VEGFA signaling impairment in SZ-hiPSC-derived neural lineages leading to decreased angiogenesis. Here, we present a functional characterization of SZ-derived brain microvascular endothelial-like cells (BEC), the counterpart of the neurovascular crosstalk, revealing an intrinsically defective blood–brain barrier (BBB) phenotype. Transcriptomic assessment of genes related to endothelial function among three control (Ctrl BEC) and five schizophrenia patients derived BEC (SZP BEC), revealed that SZP BEC have a distinctive expression pattern of angiogenic and BBB-associated genes. Functionally, SZP BEC showed a decreased angiogenic response in vitro and higher transpermeability than Ctrl BEC. Immunofluorescence staining revealed less expression and altered distribution of tight junction proteins in SZP BEC. Moreover, SZP BEC’s conditioned media reduced barrier capacities in the brain microvascular endothelial cell line HCMEC/D3 and in an in vivo permeability assay in mice. Overall, our results describe an intrinsic failure of SZP BEC for proper barrier function. These findings are consistent with the hypothesis tracing schizophrenia origins to brain development and BBB dysfunction.es
dc.description.versionVersión publicadaes
dc.identifier.citationCasas, B.S., Vitória, G., Prieto, C.P. et al. Schizophrenia-derived hiPSC brain microvascular endothelial-like cells show impairments in angiogenesis and blood–brain barrier function. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01653-0es
dc.identifier.urihttps://doi.org/10.1038/s41380-022-01653-0es
dc.identifier.urihttp://hdl.handle.net/11447/6656
dc.language.isoenes
dc.titleSchizophrenia-derived hiPSC brain microvascular endothelial-like cells show impairments in angiogenesis and blood–brain barrier functiones
dc.typeArticlees
dcterms.sourceMolecular psychiatryes

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