{"doi":"10.1016/j.stemcr.2022.12.005","title":"Unusual X chromosome inactivation maintenance in female alveolar type 2 cells is correlated with increased numbers of X-linked escape genes and sex-biased gene expression","abstract":"Sex differences exist for many lung pathologies, including COVID-19 and pulmonary fibrosis, but the mechanistic basis for this remains unclear. Alveolar type 2 cells (AT2s), which play a key role in alveolar lung regeneration, express the X-linked Ace2 gene that has roles in lung repair and SARS-CoV-2 pathogenesis, suggesting that X chromosome inactivation (XCI) in AT2s might impact sex-biased lung pathology. Here we investigate XCI maintenance and sex-specific gene expression profiles using male and female AT2s. Remarkably, the inactive X chromosome (Xi) lacks robust canonical Xist RNA \"clouds\" and less enrichment of heterochromatic modifications in human and mouse AT2s. We demonstrate that about 68% of expressed X-linked genes in mouse AT2s, including Ace2, escape XCI. There are genome-wide expression differences between male and female AT2s, likely influencing both lung physiology and pathophysiologic responses. These studies support a renewed focus on AT2s as a potential contributor to sex-biased differences in lung disease.","journal":"Stem Cell Reports","year":2023,"id":340551,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"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":403001,"name":"Sarah Pyfrom","orcid":"0000-0002-3781-6463","position":1,"is_corresponding":false},{"id":324333,"name":"Aaron I. Weiner","orcid":"0000-0003-3618-5548","position":2,"is_corresponding":false},{"id":324332,"name":"Gan Zhao","orcid":"0000-0002-8043-6036","position":3,"is_corresponding":false},{"id":1075062,"name":"Amanda J. Driscoll","orcid":"0000-0002-6320-9392","position":4,"is_corresponding":false},{"id":295582,"name":"Xiang Yu","orcid":"0000-0002-5730-8802","position":5,"is_corresponding":false},{"id":295584,"name":"Brian D. Gregory","orcid":"0000-0001-7532-0138","position":6,"is_corresponding":false},{"id":324336,"name":"Andrew E. Vaughan","orcid":"0000-0001-5740-643X","position":7,"is_corresponding":false},{"id":376544,"name":"Montserrat C. Anguera","orcid":"0000-0003-4992-3079","position":8,"is_corresponding":false},{"id":991071,"name":"Isabel Sierra","orcid":"0000-0002-4875-2741","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:10:54.145367Z","pmid":"36638790","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":[]}