biostudies-literatureCardozo PLFundação de Amparo à Pesquisa do Estado de Minas GeraisConselho Nacional de Desenvolvimento Científico e Tecnológicoe70085https://www.ebi.ac.uk/biostudies/studies/S-EPMC12666992biostudies-literatureUnknown74(1)Neuroinflammation, particularly astrocyte reactivity, is increasingly linked to schizophrenia (SCZ). Yet, the crosstalk between astrocytes and microglia in SCZ, especially under pro-inflammatory conditions, remains unclear. Here, we employed human induced-pluripotent stem cells to compare how astrocytes from five age-matched individuals with SCZ and five neurotypical controls, upon stimulation with TNF-α, affected microglial biology. TNF-α stimulation of SCZ astrocytes, relative to their control counterparts, triggered increased mRNA expression of pro-inflammatory cytokines and CX3CL1. Interestingly, transcriptomic and gene set enrichment analyses revealed that reactive SCZ astrocytes promoted the downregulation of biological processes associated with immune cell proliferation and activatiGliahiPSC-Derived Astrocytes From Individuals With Schizophrenia Induce a Dystrophic Phenotype in Microglial-Like Cells.PMC12666992APQ‐00140‐23444206/2024-8406968/2024‐1APQ-00140-23444206/2024‐8APQ‐03921‐22406968/2024-1APQ-03921-22BPD‐00067‐22403171/2023-7BPD-00067-22403171/2023‐7Bonamino MHCruz BFChicaybam LBrennand KJCardozo PLLee CYde Faria IJSVitoria GCordeiro RCTodjro YMHFahel JSSilva NCMaciel JCDPTrindade PRehen SKNicolato RLacerda JPSVieira LBRibeiro FMfalsehiPSC-Derived Astrocytes From Individuals With Schizophrenia Induce a Dystrophic Phenotype in Microglial-Like Cells.Neuroinflammation, particularly astrocyte reactivity, is increasingly linked to schizophrenia (SCZ). Yet, the crosstalk between astrocytes and microglia in SCZ, especially under pro-inflammatory conditions, remains unclear. Here, we employed human induced-pluripotent stem cells to compare how astrocytes from five age-matched individuals with SCZ and five neurotypical controls, upon stimulation with TNF-α, affected microglial biology. TNF-α stimulation of SCZ astrocytes, relative to their control counterparts, triggered increased mRNA expression of pro-inflammatory cytokines and CX3CL1. Interestingly, transcriptomic and gene set enrichment analyses revealed that reactive SCZ astrocytes promoted the downregulation of biological processes associated with immune cell proliferation and activati2026-01-01T00:00:00Z2026 Jan2026-06-05T20:39:37.495Z2026-05-21T03:13:02.043ZS-EPMC126669924097046810.1002/glia.70085