Induced pluripotent stem cell-derived astrocytes from patients with schizophrenia exhibit an inflammatory phenotype that affects vascularization

• DOI: 10.1038/s41380-022-01830-1
• Publication Date: 2022-10-24T07:02:49Z
• Authors: Pablo Trindade; Juliana Minardi N...; Bárbara S. Casas; Tomás Monteverde; Juciano Gasparotto; Camila Tiefensee ...; Sylvie Devalle; Daniela Sauma; José Claudio Fons...; Daniel Pens Gelain; Lisiane O. Porciu...; Verónica Palma; Daniel Martins-de...; Stevens K. Rehen
• Keywords: Proteomics; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Tumor Necrosis Factor-alpha; Astrocytes; Induced Pluripotent Stem Cells; Schizophrenia; Humans; Cytokines

SummaryMolecular and functional abnormalities of astrocytes have been implicated in the etiology and pathogenesis of schizophrenia (SCZ). In this study, we examined the proteome, inflammatory responses, and secretome effects on vascularization of human induced pluripotent stem cell (hiPSC)-derived astrocytes from patients with SCZ. Proteomic analysis revealed alterations in proteins related to immune function and vascularization. Reduced expression of the nuclear factor kappa B (NF-κB) p65 subunit was observed in these astrocytes, with no incremental secretion of cytokines after tumor necrosis factor alpha (TNF-α) stimulation. Among inflammatory cytokines, secretion of interleukin (IL)-8 was found particularly elevated in SCZ-patient-derived– astrocyte conditioned medium (ASCZCM). In a chicken chorioallantoic membrane (CAM) assay, ASCZCM reduced the diameter of newly grown vessels, and this effect could be mimicked with exogenous addition of IL-8. Taken together, our results suggest that SCZ astrocytes are immunologically dysfunctional and may consequently affect vascularization through secreted factors.