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A Single Cell Atlas of Lung Development

View ORCID ProfileNicholas M. Negretti, View ORCID ProfileErin J. Plosa, John T. Benjamin, View ORCID ProfileBryce A. Schuler, View ORCID ProfileA. Christian Habermann, Christopher Jetter, Peter Gulleman, Chase J. Taylor, David Nichols, Brittany K. Matlock, View ORCID ProfileSusan H. Guttentag, Timothy S. Blackwell, View ORCID ProfileNicholas E. Banovich, View ORCID ProfileJonathan A. Kropski, View ORCID ProfileJennifer M. S. Sucre
doi: https://doi.org/10.1101/2021.01.21.427641
Nicholas M. Negretti
1Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
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Erin J. Plosa
1Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
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John T. Benjamin
1Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
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Bryce A. Schuler
1Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
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A. Christian Habermann
2Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
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Christopher Jetter
1Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
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Peter Gulleman
1Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
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Chase J. Taylor
2Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
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David Nichols
2Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
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Brittany K. Matlock
3Flow Cytometry Shared Resource, Vanderbilt University Medical Center, Nashville, TN
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Susan H. Guttentag
1Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
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Timothy S. Blackwell
2Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
4Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN
5Department of Veterans Affairs Medical Center, Nashville, TN
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Nicholas E. Banovich
6Translational Genomics Research Institute, Phoenix, AZ
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Jonathan A. Kropski
2Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
4Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN
5Department of Veterans Affairs Medical Center, Nashville, TN
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  • For correspondence: jennifer.sucre@vumc.org jon.kropski@vumc.org
Jennifer M. S. Sucre
1Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
4Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN
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  • For correspondence: jennifer.sucre@vumc.org jon.kropski@vumc.org
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Summary

Lung organogenesis requires precisely timed shifts in the spatial organization and function of parenchymal cells, especially during the later stages of lung development. To investigate the mechanisms governing lung parenchymal dynamics during development, we performed a single cell RNA sequencing (scRNA-seq) time-series yielding 92,238 epithelial, endothelial, and mesenchymal cells across 8 time points from embryonic day 12 (E12) to postnatal day 14 (P14) in mice. We combined new computational analyses with RNA in situ hybridization to explore transcriptional velocity, fate likelihood prediction, and spatiotemporal localization of cell populations during the transition between the saccular and alveolar stages. We interrogated this atlas to illustrate the complexity of type 1 pneumocyte function during the saccular and alveolar stages, and we demonstrate an integrated view of the cellular dynamics during lung development.

Competing Interest Statement

JAK has received advisory board fees from Boehringer Ingelheim, Inc and Janssen Therapeutics, grants from Boehringer Ingelheim, Inc, and has research contracts with Genentech. TSB has received advisory board fees from Boehringer Ingelheim, Inc, Orinove, GRI Bio, Morphic, and Novelstar, and has research contracts with Genentech and Celgene.

Footnotes

  • Supplemental files updated.

  • https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE160876

  • https://github.com/SucreLab/LungDevelopment

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 25, 2021.
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A Single Cell Atlas of Lung Development
Nicholas M. Negretti, Erin J. Plosa, John T. Benjamin, Bryce A. Schuler, A. Christian Habermann, Christopher Jetter, Peter Gulleman, Chase J. Taylor, David Nichols, Brittany K. Matlock, Susan H. Guttentag, Timothy S. Blackwell, Nicholas E. Banovich, Jonathan A. Kropski, Jennifer M. S. Sucre
bioRxiv 2021.01.21.427641; doi: https://doi.org/10.1101/2021.01.21.427641
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A Single Cell Atlas of Lung Development
Nicholas M. Negretti, Erin J. Plosa, John T. Benjamin, Bryce A. Schuler, A. Christian Habermann, Christopher Jetter, Peter Gulleman, Chase J. Taylor, David Nichols, Brittany K. Matlock, Susan H. Guttentag, Timothy S. Blackwell, Nicholas E. Banovich, Jonathan A. Kropski, Jennifer M. S. Sucre
bioRxiv 2021.01.21.427641; doi: https://doi.org/10.1101/2021.01.21.427641

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