A molecular cell atlas of the human lung from single-cell RNA sequencing (2023)

Travaglini, K. J., Nabhan, A. N., Penland, L., Sinha, R., Gillich, A., Sit, R. V., Chang, S., Conley, S. D., Mori, Y., Seita, J., Berry, G. J., Shrager, J. B., Metzger, R. J., Kuo, C. S., Neff, N., Weissman, I. L., Quake, S. R., & Krasnow, M. A. (2020). A molecular cell atlas of the human lung from single-cell RNA sequencing. Nature, 587(7835), 619-625. https://doi.org/10.1038/s41586-020-2922-4

A molecular cell atlas of the human lung from single-cell RNA sequencing. / Travaglini, Kyle J.; Nabhan, Ahmad N.; Penland, Lolita et al.
In: Nature, Vol. 587, No. 7835, 26.11.2020, p. 619-625.

Research output: Contribution to journal › Article › peer-review

Travaglini, KJ, Nabhan, AN, Penland, L, Sinha, R, Gillich, A, Sit, RV, Chang, S, Conley, SD, Mori, Y, Seita, J, Berry, GJ, Shrager, JB, Metzger, RJ, Kuo, CS, Neff, N, Weissman, IL, Quake, SR & Krasnow, MA 2020, 'A molecular cell atlas of the human lung from single-cell RNA sequencing', Nature, vol. 587, no. 7835, pp. 619-625. https://doi.org/10.1038/s41586-020-2922-4

Travaglini KJ, Nabhan AN, Penland L, Sinha R, Gillich A, Sit RV et al. A molecular cell atlas of the human lung from single-cell RNA sequencing. Nature. 2020 Nov 26;587(7835):619-625. doi: 10.1038/s41586-020-2922-4

Travaglini, Kyle J. ; Nabhan, Ahmad N. ; Penland, Lolita et al. / A molecular cell atlas of the human lung from single-cell RNA sequencing. In: Nature. 2020 ; Vol. 587, No. 7835. pp. 619-625.

@article{610e131a2f1b4ccaa5e4191bb7e01888,

title = "A molecular cell atlas of the human lung from single-cell RNA sequencing",

abstract = "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 molecularcell 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.",

author = "Travaglini, {Kyle J.} and Nabhan, {Ahmad N.} and Lolita Penland and Rahul Sinha and Astrid Gillich and Sit, {Rene V.} and Stephen Chang and Conley, {Stephanie D.} and Yasuo Mori and Jun Seita and Berry, {Gerald J.} and Shrager, {Joseph B.} and Metzger, {Ross J.} and Kuo, {Christin S.} and Norma Neff and Weissman, {Irving L.} and Quake, {Stephen R.} and Krasnow, {Mark A.}",

note = "Funding Information: Acknowledgements We are grateful to the tissue donors and the clinical staff at Stanford Medical Center who made tissue collection possible, especially J. Benson and E. Chen. We are especially grateful to Jim Spudich who spurred this study. We also thank the Stanford Shared FACS Facility for their expertise and sorting services, especially L. Nichols and M. Weglarz; members of Chan Zuckerberg Biohub and Quake laboratory who supported this work, particularly A. McGeever, B.Yu, B. Jones and S. Kolluru; M. Kumar for discussions on annotation of stromal cells; and M. Petersen for illustrating the lung schematic (Fig. 1b) and C. Kao for help with figure formatting. Some computing for this project was performed on the Sherlock cluster; we thank Stanford University and the Stanford Research Computing Center for providing computational resources and support that contributed to the results. We thank J. Spudich and members of the Krasnow laboratory for discussions and comments on the manuscript, and A. Lozano for discussions on bioinformatic analyses. This work was supported by funding from the Chan Zuckerberg Biohub (S.R.Q.), the Howard Hughes Medical Institute, National Institutes of Health, and the Vera Moulton Wall Center for Pulmonary Vascular Disease (M.A.K.), and the Ludwig Cancer Center at Stanford (I.L.W.). K.J.T was supported by a Paul and Mildred Berg Stanford Graduate Fellowship. M.A.K. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2020",

month = nov,

day = "26",

doi = "10.1038/s41586-020-2922-4",

language = "English",

volume = "587",

pages = "619--625",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7835",

}

TY - JOUR

T1 - A molecular cell atlas of the human lung from single-cell RNA sequencing

AU - Travaglini, Kyle J.

AU - Nabhan, Ahmad N.

AU - Penland, Lolita

AU - Sinha, Rahul

AU - Gillich, Astrid

AU - Sit, Rene V.

AU - Chang, Stephen

AU - Conley, Stephanie D.

AU - Mori, Yasuo

AU - Seita, Jun

AU - Berry, Gerald J.

AU - Shrager, Joseph B.

AU - Metzger, Ross J.

AU - Kuo, Christin S.

AU - Neff, Norma

AU - Weissman, Irving L.

AU - Quake, Stephen R.

AU - Krasnow, Mark A.

N1 - Funding Information:Acknowledgements We are grateful to the tissue donors and the clinical staff at Stanford Medical Center who made tissue collection possible, especially J. Benson and E. Chen. We are especially grateful to Jim Spudich who spurred this study. We also thank the Stanford Shared FACS Facility for their expertise and sorting services, especially L. Nichols and M. Weglarz; members of Chan Zuckerberg Biohub and Quake laboratory who supported this work, particularly A. McGeever, B.Yu, B. Jones and S. Kolluru; M. Kumar for discussions on annotation of stromal cells; and M. Petersen for illustrating the lung schematic (Fig. 1b) and C. Kao for help with figure formatting. Some computing for this project was performed on the Sherlock cluster; we thank Stanford University and the Stanford Research Computing Center for providing computational resources and support that contributed to the results. We thank J. Spudich and members of the Krasnow laboratory for discussions and comments on the manuscript, and A. Lozano for discussions on bioinformatic analyses. This work was supported by funding from the Chan Zuckerberg Biohub (S.R.Q.), the Howard Hughes Medical Institute, National Institutes of Health, and the Vera Moulton Wall Center for Pulmonary Vascular Disease (M.A.K.), and the Ludwig Cancer Center at Stanford (I.L.W.). K.J.T was supported by a Paul and Mildred Berg Stanford Graduate Fellowship. M.A.K. is an investigator of the Howard Hughes Medical Institute.Publisher Copyright:© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2020/11/26

Y1 - 2020/11/26

N2 - 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 molecularcell 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.

AB - 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 molecularcell 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.

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U2 - 10.1038/s41586-020-2922-4

DO - 10.1038/s41586-020-2922-4

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