{"doi":"10.7554/elife.65856","title":"CRISPR-based functional genomics in human dendritic cells","abstract":"Dendritic cells (DCs) regulate processes ranging from antitumor and antiviral immunity to host-microbe communication at mucosal surfaces. It remains difficult, however, to genetically manipulate human DCs, limiting our ability to probe how DCs elicit specific immune responses. Here, we develop a CRISPR-Cas9 genome editing method for human monocyte-derived DCs (moDCs) that mediates knockouts with a median efficiency of >94% across >300 genes. Using this method, we perform genetic screens in moDCs, identifying mechanisms by which DCs tune responses to lipopolysaccharides from the human microbiome. In addition, we reveal donor-specific responses to lipopolysaccharides, underscoring the importance of assessing immune phenotypes in donor-derived cells, and identify candidate genes that control this specificity, highlighting the potential of our method to pinpoint determinants of inter-individual variation in immunity. Our work sets the stage for a systematic dissection of the immune signaling at the host-microbiome interface and for targeted engineering of DCs for neoantigen vaccination.","journal":"eLife","year":2021,"id":170815,"datarank":0.9174675152541587,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.41763683872787805,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.41763683872787805,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":27,"citers_with_citation_signal":24,"citers_with_endowment":24,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE161401","GSE161466"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":703899,"name":"Amy N. Jacobson","orcid":"0000-0001-6518-5446","position":1,"is_corresponding":false},{"id":227001,"name":"Jeffrey A. Hussmann","orcid":"0000-0002-7778-9893","position":2,"is_corresponding":false},{"id":259935,"name":"Giana Cirolia","orcid":"0000-0002-9407-8495","position":3,"is_corresponding":false},{"id":44570,"name":"Michael A. Fischbach","orcid":"0000-0003-3079-8247","position":4,"is_corresponding":false},{"id":17890,"name":"Jonathan S. Weissman","orcid":"0000-0003-2445-670X","position":5,"is_corresponding":false},{"id":251069,"name":"Marco Jost","orcid":"0000-0002-1369-4908","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:46:24.040760Z","pmid":"33904395","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":[]}