{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:48:48Z","timestamp":1790380128182,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"Office of the Director","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL155104"],"award-info":[{"award-number":["R01HL155104"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["R21HL165411"],"award-info":[{"award-number":["R21HL165411"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["R01HL141856"],"award-info":[{"award-number":["R01HL141856"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R24HD000836"],"award-info":[{"award-number":["R24HD000836"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Trisomy 21 (T21), resulting in Down syndrome (DS), is the most prevalent chromosomal abnormality worldwide. While pulmonary disease is a major cause of morbidity and mortality in DS, the ontogeny of pulmonary complications remains poorly understood. We recently demonstrated that T21 lung anomalies, including airway branching and vascular lymphatic \u00adabnormalities, are initiated in utero. Here, we aimed to describe molecular changes at the single-cell level in prenatal T21 lungs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-cell RNA sequencing was used to generate transcriptomic profiles of individual human lung cells in tissue obtained from T21 (n\u2009=\u20095) and non-T21 (n\u2009=\u20094) prenatal lungs. Clustering of cells, marker identification, uniform manifold approximation and projection representation, and differential expression analysis were performed in Seurat. Cell type annotation and pathway analysis were annotated using ToppFun and a human fetal lung cell atlas. Spatial differences in cellular phenotypes were validated using immunofluorescence staining and fluorescent in situ hybridization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results detail changes in gene expression at the time of initiation of histopathological abnormalities in T21 prenatal lungs. Notably, we identify precocious differentiation of epithelial cells, widespread induction of key extracellular matrix molecules in mesenchymal cells, and hyperactivation of IFN signaling in endothelial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This single-cell dataset of T21 lungs greatly expands our understanding of antecedents to pulmonary complications and should facilitate efforts to mitigate respiratory disease in DS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1165\/rcmb.2025-0217oc","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T17:32:54Z","timestamp":1758821574000},"page":"388-402","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":4,"title":["The transcriptional landscape of developing human trisomy 21 lungs"],"prefix":"10.1093","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1140-7845","authenticated-orcid":false,"given":"Soumyaroop","family":"Bhattacharya","sequence":"first","affiliation":[{"name":"Center for Children\u2019s Health Research, University of Rochester Medical Center , Rochester, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Frauenpreis","sequence":"additional","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center , Torrance, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Cherry","sequence":"additional","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center , Torrance, CA,","place":["United 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