Journal Article DZNE-2023-00690

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An integrated cell atlas of the lung in health and disease.

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2023
Nature America Inc. New York, NY

Nature medicine 29(6), 1563 - 1577 () [10.1038/s41591-023-02327-2]

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Abstract: Single-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.

Keyword(s): Humans (MeSH) ; COVID-19 (MeSH) ; Lung (MeSH) ; Pulmonary Fibrosis (MeSH) ; Lung Neoplasms: genetics (MeSH) ; Macrophages (MeSH)

Classification:

Contributing Institute(s):
  1. Platform for Single Cell Genomics and Epigenomics (Schultze - PRECISE)
  2. Platform for Single Cell Genomics and Epigenomics at DZNE & University of Bonn (R&D PRECISE)
Research Program(s):
  1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
  2. 352 - Disease Mechanisms (POF4-352) (POF4-352)
Experiment(s):
  1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2023
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Medline ; Creative Commons Attribution CC BY 4.0 ; OpenAccess ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 80 ; JCR ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Institute Collections > BN DZNE > BN DZNE-R&D PRECISE
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Institute Collections > BN DZNE > BN DZNE-PRECISE
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 Record created 2023-07-03, last modified 2023-10-04