A molecular cell atlas of the human lung from single cell RNA sequencing

By K. Travaglini, Ahmad N. Nabhan, L. Penland, Rahul Sinha, A. Gillich, R. Sit, Stephen Chang, Stephanie D. Conley, Y. Mori, J. Seita and 8 more. Nature, 2019

1,372 citations recorded by the source corpus.

Although single-cell RNA sequencing studies have begun to provide compendia of cell expression profiles1–9, it has been difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here, using droplet- and plate-based single-cell RNA sequencing of approximately 75,000 human cells across all lung tissue compartments and circulating blood, combined with a multi-pronged cell annotation approach, we create an extensive cell atlas of the human lung. We define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 out of 45 previously known cell types and 14 previously unknown ones. This comprehensive molecular atlas identifies the biochemical functions of lung cells and the transcription factors and markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signalling interactions and immune cell homing; and identifies cell types that are directly affected by lung disease genes and respiratory viruses. By comparing human and mouse data, we identified 17 molecular cell types that have been gained or lost during lung evolution and others with substantially altered expression profiles, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions and interactions are achieved in development and tissue engineering and altered in disease and evolution. Expression profiling on 75,000 single cells creates a comprehensive cell atlas of the human lung that includes 41 out of 45 previously known cell types and 14 new ones.

Subfields: Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/056a4484d54bbc5d5a014ecd5530c21a062b95c0

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In Molecular Biology

1. Roser Vento-Tormo
2. Oliver Stegle
3. E. Dann
4. Moritz Gerstung
5. Hamish W. King
6. Adam Gayoso
7. John C. Marioni

Citations in the corpus

• Cell2location maps fine-grained cell types in spatial transcriptomics (2022, methodology): “Cell atlasing studies have greatly expanded the catalog of fine-grained cell types across human tissues, which are often of key interest for understanding tissue function and pathology 7,9,11 .”
• Immunology of COVID-19: Current State of the Science (2020, positive): “, 2009), lung NK cells do not express the entry receptor for SARS-CoV2, ACE2, and are therefore unlikely to be directly infected by SARS-CoV-2 (Travaglini et al., 2020).”
• Dictionary learning for integrative, multimodal, and massively scalable single-cell analysis (2022, neutral): “We computed metrics on two datasets: a 33,000-cell dataset of human PBMCs publicly available from 10x Genomics (https://support.10xgenomics.com/ single-cell-gene-expression/datasets/1.1.0/pbmc33k) and a 66,000-cell lung scRNA-seq dataset 98 .”