GEOTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298027GEOGSEfalseA Conserved NLRC5 Signaling Pathway in Developing Human Cortical Neurons is Required for Interferon Gamma Driven Changes in HLA Class I Expression and Neural ActivityMaternal infection and inflammation are linked to increased risk of neurodevelopmental disorders. Here we show that MHC Class I molecules (human: HLA I), which play key roles in brain development, are expressed in neurons in human cortical organoids (hCOs) and human cerebral cortex. These HLA I molecules are significantly upregulated by interferon gamma (IFNg) exposure. Inflammatory mediators downstream of IFNg, including the HLA I enhancer NLRC5, are mechanistically implicated in this upregulation by RNA sequencing IsHhHHLA. NLRC5 KO hCOs fail to undergo developmental increases in neuronal HLA I expression, as well as IFNg-driven HLA I upregulation. Functionally, IFNg exposure lowers spontaneous neural activity in hCOs, which is prevented in NLRC5 KO. These observations link IFNg to human neuronal HLA I expression via NLRC5 and demonstrate a functional consequence on spontaneous activity in a developing neural circuit. Changes in levels and patterns of neural activity associated with elevated HLA I may contribute to the increased risk of altered cortical development and suggest that targeting NLRC5 could mitigate consequences of neuroinflammation.2026/05/04GSE298027GSM9004971GSM9004970GSM9004973GSM9004972GSM9004975GSM9004964GSM9004974GSM9004963GSM9004977GSM9004966GSM9004976GSM9004965GSM9004968GSM9004967GSM900496924676298027Homo sapiens