{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE323nnn/GSE323982/"]},"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=GSE323982"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"MEF2C controls lysosomal and lipid clearance programs linked to Alzheimer’s disease risk in macrophagesm [scRNAseq_WTC11_iMGL_ReN]","description":"Risk alleles for late-onset Alzheimer’s disease (AD) are enriched in myeloid cis-regulatory elements, implicating myeloid gene-regulatory networks in disease susceptibility. A conserved lipid-associated transcriptional signature—spanning disease-associated microglia and peripheral lipid-associated macrophages (DLAM)—emerges across neurodegenerative and metabolic diseases, yet the transcriptional regulators of this gene expression program remain incompletely defined. Here, we show that MEF2C—a candidate AD risk gene—is a master DLAM regulator. Using MEF2C knockout and knockdown in human iPSC-derived microglia and macrophages, we found that total or partial MEF2C loss is sufficient to induce DLAM-associated transcriptional, epigenomic, and functional remodeling, including enhanced lysosomal activity and cholesterol efflux. Integration of chromatin accessibility and regulatory epigenetic profiles with functionally informed fine-mapping linked AD causal variants in other loci to MEF2C-regulated regulatory regions and downstream risk genes. In a triculture model of AD, microglial MEF2C loss is associated with an increased DLAM population and a reduced Aβ42/40 ratio, supporting context-dependent reprogramming of microglia as a mechanism to modulate AD-relevant pathology.","dates":{"publication":"2026/08/06"},"accession":"GSE323982","cross_references":{"GSM":["GSM9566062","GSM9566061","GSM9566060","GSM9566059","GSM9566058","GSM9566057","GSM9566067","GSM9566056","GSM9566066","GSM9566055","GSM9566065","GSM9566054","GSM9566053","GSM9566064","GSM9566063","GSM9566052"],"GPL":["34281"],"GSE":["323982"],"taxon":["Homo sapiens"],"PMID":["[42094058]"]}}