{"doi":"10.1101/2023.08.25.554654","title":"The cGAS-STING pathway regulates microglial chemotaxis in genome instability","abstract":"ABSTRACT Defective DNA damage signalling and repair is a hallmark of age-related and genetic neurodegenerative disease. One mechanism implicated in disease progression is DNA damage-driven neuroinflammation, which is largely mediated by tissue-resident immune cells, microglia. Here, we utilise human microglia-like cell models of persistent DNA damage and ATM kinase deficiency to investigate how genome instability shapes microglial function. We demonstrate that upon DNA damage the cytosolic DNA sensing cGAS-STING axis drives chronic inflammation and a robust chemokine response, exemplified by production of CCL5 and CXCL10. Transcriptomic analyses revealed that cell migratory pathways were highly enriched upon IFN-β treatment of human iPSC-derived microglia, indicating that the chemokine response to DNA damage mirrors type I interferon signalling. Furthermore, we find that STING deletion leads to a defect in microglial chemotaxis under basal conditions and upon ATM kinase loss. Overall, this work provides mechanistic insights into cGAS-STING-dependent neuroinflammatory mechanisms and consequences of genome instability in the central nervous system.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400561,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":941324,"name":"Lisha Joshi","orcid":"0000-0003-2714-6686","position":1,"is_corresponding":false},{"id":828034,"name":"Peter Thornton","orcid":"0000-0002-2489-3507","position":2,"is_corresponding":false},{"id":1177374,"name":"Mahya Dezfouli","orcid":null,"position":3,"is_corresponding":false},{"id":54480,"name":"Kalliopi Tsafou","orcid":null,"position":4,"is_corresponding":false},{"id":1177046,"name":"Michael S. Perkinton","orcid":"0000-0003-1130-7844","position":5,"is_corresponding":false},{"id":883440,"name":"S. V. Khoronenkova","orcid":"0000-0002-7439-9320","position":6,"is_corresponding":false},{"id":883438,"name":"Emily Talbot","orcid":"0000-0002-5951-8862","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:04.010538Z","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":[]}