{"doi":"10.1016/j.celrep.2025.115909","title":"Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypes in vitro","abstract":"Myeloid cells, including brain-resident microglia and peripheral macrophages, play key roles in neurodegenerative diseases such as Alzheimer's disease (AD). Studying their disease-associated states is limited by the lack of robust in vitro models. Here, we test whether a cytokine mix (interleukin [IL]-4, CSF1, IL-34, and transforming growth factor-β) reprograms human THP-1 macrophages toward AD-relevant phenotypes. This treatment induces significant transcriptomic changes, driving THP-1 macrophages toward a transcriptional state reminiscent of disease-associated microglia and lipid-associated macrophages (LAM), collectively referred to as DLAM. Transcriptome profiling reveals gene expression changes related to oxidative phosphorylation, lysosome function, and lipid metabolism. Single-cell RNA sequencing shows an increased proportion of DLAM clusters in cytokine mix-treated THP-1 macrophages. Functional assays demonstrate alterations in cell motility, phagocytosis, lysosomal activity, and metabolic profiles. These findings provide insights into cytokine-mediated reprogramming of macrophages toward disease-relevant states, highlighting their role in neurodegenerative diseases and potential for therapeutic development.","journal":"Cell Reports","year":2025,"id":523708,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1045191,"name":"Carmen Romero‐Molina","orcid":"0000-0002-3119-961X","position":1,"is_corresponding":false},{"id":308846,"name":"Tulsi Patel","orcid":"0000-0002-2797-1443","position":2,"is_corresponding":false},{"id":1356696,"name":"Wen Yi See","orcid":null,"position":3,"is_corresponding":false},{"id":626242,"name":"Yiyuan Liu","orcid":"0000-0002-9008-9170","position":4,"is_corresponding":false},{"id":236141,"name":"Edoardo Marcora","orcid":"0000-0002-3829-4927","position":5,"is_corresponding":false},{"id":27629,"name":"Alison Goate","orcid":"0000-0002-0576-2472","position":6,"is_corresponding":false},{"id":1014297,"name":"Anna Podlesny‐Drabiniok","orcid":"0000-0001-5009-2263","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T02:50:07.396155Z","pmid":"40570367","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":[]}