000258918 001__ 258918 000258918 005__ 20231004134651.0 000258918 0247_ $$2doi$$a10.1038/s41591-023-02327-2 000258918 0247_ $$2pmid$$apmid:37291214 000258918 0247_ $$2pmc$$apmc:PMC10287567 000258918 0247_ $$2ISSN$$a1078-8956 000258918 0247_ $$2ISSN$$a1546-170X 000258918 0247_ $$2altmetric$$aaltmetric:149752437 000258918 037__ $$aDZNE-2023-00690 000258918 041__ $$aEnglish 000258918 082__ $$a610 000258918 1001_ $$00000-0001-9686-6295$$aSikkema, Lisa$$b0 000258918 245__ $$aAn integrated cell atlas of the lung in health and disease. 000258918 260__ $$aNew York, NY$$bNature America Inc.$$c2023 000258918 3367_ $$2DRIVER$$aarticle 000258918 3367_ $$2DataCite$$aOutput Types/Journal article 000258918 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1692960345_28577 000258918 3367_ $$2BibTeX$$aARTICLE 000258918 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000258918 3367_ $$00$$2EndNote$$aJournal Article 000258918 520__ $$aSingle-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas. 000258918 536__ $$0G:(DE-HGF)POF4-354$$a354 - Disease Prevention and Healthy Aging (POF4-354)$$cPOF4-354$$fPOF IV$$x0 000258918 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x1 000258918 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000258918 650_2 $$2MeSH$$aHumans 000258918 650_2 $$2MeSH$$aCOVID-19 000258918 650_2 $$2MeSH$$aLung 000258918 650_2 $$2MeSH$$aPulmonary Fibrosis 000258918 650_2 $$2MeSH$$aLung Neoplasms: genetics 000258918 650_2 $$2MeSH$$aMacrophages 000258918 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE University of Bonn$$x0 000258918 7001_ $$aRamírez-Suástegui, Ciro$$b1 000258918 7001_ $$aStrobl, Daniel C$$b2 000258918 7001_ $$00000-0002-5447-1727$$aGillett, Tessa E$$b3 000258918 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