{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE298nnn/GSE298027/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298027"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A Conserved NLRC5 Signaling Pathway in Developing Human Cortical Neurons is Required for Interferon Gamma Driven Changes in HLA Class I Expression and Neural Activity","description":"Maternal 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.","dates":{"publication":"2026/05/04"},"accession":"GSE298027","cross_references":{"GSM":["GSM9004971","GSM9004970","GSM9004973","GSM9004972","GSM9004975","GSM9004964","GSM9004974","GSM9004963","GSM9004977","GSM9004966","GSM9004976","GSM9004965","GSM9004968","GSM9004967","GSM9004969"],"GPL":["24676"],"GSE":["298027"],"taxon":["Homo sapiens"]}}