{"doi":"10.1016/j.cell.2023.08.037","title":"Human microglial state dynamics in Alzheimer’s disease progression","abstract":"Altered microglial states affect neuroinflammation, neurodegeneration, and disease but remain poorly understood. Here, we report 194,000 single-nucleus microglial transcriptomes and epigenomes across 443 human subjects and diverse Alzheimer's disease (AD) pathological phenotypes. We annotate 12 microglial transcriptional states, including AD-dysregulated homeostatic, inflammatory, and lipid-processing states. We identify 1,542 AD-differentially-expressed genes, including both microglia-state-specific and disease-stage-specific alterations. By integrating epigenomic, transcriptomic, and motif information, we infer upstream regulators of microglial cell states, gene-regulatory networks, enhancer-gene links, and transcription-factor-driven microglial state transitions. We demonstrate that ectopic expression of our predicted homeostatic-state activators induces homeostatic features in human iPSC-derived microglia-like cells, while inhibiting activators of inflammation can block inflammatory progression. Lastly, we pinpoint the expression of AD-risk genes in microglial states and differential expression of AD-risk genes and their regulators during AD progression. Overall, we provide insights underlying microglial states, including state-specific and AD-stage-specific microglial alterations at unprecedented resolution.","journal":"Cell","year":2023,"id":6514,"datarank":0.8929865001431678,"base_score":5.953243334287785,"endowment":5.953243334287785,"self_citation_contribution":0.8929865001431678,"citation_network_contribution":0.0,"self_endowment_contribution":0.8929865001431678,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":384,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.2787,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-09-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":11603,"name":"Matheus B. Victor","orcid":"0000-0003-4364-4028","position":1,"is_corresponding":false},{"id":7736,"name":"Yongjin P. Park","orcid":"0000-0001-8915-2876","position":2,"is_corresponding":false},{"id":7415,"name":"Xushen Xiong","orcid":"0000-0001-7090-7503","position":3,"is_corresponding":false},{"id":60334,"name":"Aine Ni Scannail","orcid":null,"position":4,"is_corresponding":false},{"id":71429,"name":"Gloria Suella Menchaca","orcid":null,"position":5,"is_corresponding":false},{"id":60335,"name":"Shaniah Prosper","orcid":null,"position":6,"is_corresponding":false},{"id":60336,"name":"Soujanya Viswanathan","orcid":null,"position":7,"is_corresponding":false},{"id":60337,"name":"Xochitl Luna","orcid":null,"position":8,"is_corresponding":false},{"id":4960,"name":"Carles B. Adsera","orcid":"0000-0001-9212-856X","position":9,"is_corresponding":false},{"id":39697,"name":"Benjamin T. James","orcid":"0000-0002-6228-055X","position":10,"is_corresponding":false},{"id":12683,"name":"Yosuke Tanigawa","orcid":"0000-0001-9759-157X","position":11,"is_corresponding":false},{"id":24159,"name":"Kyriaki Galani","orcid":null,"position":12,"is_corresponding":false},{"id":17177,"name":"Hansruedi Mathys","orcid":"0000-0003-0186-2115","position":13,"is_corresponding":false},{"id":24160,"name":"Xueqiao Jiang","orcid":"0000-0001-8073-1636","position":14,"is_corresponding":false},{"id":24161,"name":"Ayesha P. Ng","orcid":"0000-0001-8283-4436","position":15,"is_corresponding":false},{"id":778,"name":"David A. Bennett","orcid":"0000-0003-3689-554X","position":16,"is_corresponding":false},{"id":11618,"name":"Li-Huei Tsai","orcid":"0000-0003-1262-0592","position":17,"is_corresponding":false},{"id":14693,"name":"Sharon L. R. Kardia","orcid":"0000-0002-9853-3379","position":18,"is_corresponding":false},{"id":11597,"name":"Na Sun","orcid":"0000-0002-9540-8206","position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}