{"doi":"10.1101/2024.03.18.585578","title":"Stable and robust Xi and Y transcriptomes drive cell-type-specific autosomal and Xa responses <i>in vivo</i> and <i>in vitro</i> in four human cell types","abstract":"Summary Recent in vitro studies of human sex chromosome aneuploidy showed that the Xi (“inactive” X) and Y chromosomes broadly modulate autosomal and Xa (“active” X) gene expression in two cell types. We tested these findings in vivo in two additional cell types. Using linear modeling in CD4+ T cells and monocytes from individuals with one to three X chromosomes and zero to two Y chromosomes, we identified 82 sex-chromosomal and 344 autosomal genes whose expression changed significantly with Xi and/or Y dosage in vivo . Changes in sex-chromosomal expression were remarkably constant in vivo and in vitro across all four cell types examined. In contrast, autosomal responses to Xi and/or Y dosage were largely cell-type-specific, with up to 2.6-fold more variation than sex-chromosomal responses. Targets of the X- and Y-encoded transcription factors ZFX and ZFY accounted for a significant fraction of these autosomal responses both in vivo and in vitro . We conclude that the human Xi and Y transcriptomes are surprisingly robust and stable across the four cell types examined, yet they modulate autosomal and Xa genes – and cell function – in a cell-type-specific fashion. These emerging principles offer a foundation for exploring the wide-ranging regulatory roles of the sex chromosomes across the human body.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490411,"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":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":806475,"name":"Adrianna K. San Roman","orcid":"0000-0003-4511-3052","position":1,"is_corresponding":false},{"id":335612,"name":"Geryl Wood","orcid":null,"position":2,"is_corresponding":false},{"id":500859,"name":"Ashley Buscetta","orcid":"0000-0002-4563-2509","position":3,"is_corresponding":false},{"id":693726,"name":"Nicole Banks","orcid":"0000-0003-4277-5368","position":4,"is_corresponding":false},{"id":65486,"name":"Helen Skaletsky","orcid":"0000-0002-2724-3673","position":5,"is_corresponding":false},{"id":550248,"name":"Alexander K. Godfrey","orcid":"0000-0002-5681-3225","position":6,"is_corresponding":false},{"id":1225955,"name":"Thao T. Pham","orcid":"0009-0000-8297-0374","position":7,"is_corresponding":false},{"id":551730,"name":"Jennifer F. Hughes","orcid":"0000-0001-6590-7867","position":8,"is_corresponding":false},{"id":960293,"name":"Laura Brown","orcid":"0000-0002-7590-7323","position":9,"is_corresponding":false},{"id":394865,"name":"Paul Kruszka","orcid":"0000-0003-4949-0875","position":10,"is_corresponding":false},{"id":317599,"name":"Angela E. Lin","orcid":"0000-0002-1145-4572","position":11,"is_corresponding":false},{"id":218272,"name":"Daniel L. Kastner","orcid":"0000-0001-7188-4550","position":12,"is_corresponding":false},{"id":394864,"name":"Maximilian Muenke","orcid":"0000-0002-7719-6545","position":13,"is_corresponding":false},{"id":183555,"name":"David C. Page","orcid":"0000-0001-5489-6453","position":14,"is_corresponding":false},{"id":806476,"name":"Laura V. Blanton","orcid":"0000-0002-8975-1681","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:37.162700Z","pmid":"38562807","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":[]}