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Form and function: diverse homeostatic and immunomodulatory roles of immune cells in the developing lung revealed at single cell resolution

View ORCID ProfileRacquel Domingo-Gonzalez, View ORCID ProfileFabio Zanini, Xibing Che, Min Liu, Robert C. Jones, Michael A. Swift, Stephen R. Quake, View ORCID ProfileDavid N. Cornfield, View ORCID ProfileCristina M. Alvira
doi: https://doi.org/10.1101/2020.02.10.942359
Racquel Domingo-Gonzalez
1Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
2Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, CA
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  • ORCID record for Racquel Domingo-Gonzalez
Fabio Zanini
3Department of Bioengineering, Stanford University, Stanford, CA
4Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia
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Xibing Che
1Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
2Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, CA
5Division of Pulmonary, Asthma and Sleep Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
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Min Liu
1Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
2Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, CA
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Robert C. Jones
3Department of Bioengineering, Stanford University, Stanford, CA
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Michael A. Swift
6Department of Chemical and Systems Biology, Stanford University, Stanford CA
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Stephen R. Quake
3Department of Bioengineering, Stanford University, Stanford, CA
7Chan Zuckerberg Biohub, San Francisco, CA
8Department of Applied Physics, Stanford University, Stanford, CA
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David N. Cornfield
1Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
2Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, CA
5Division of Pulmonary, Asthma and Sleep Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
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Cristina M. Alvira
1Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
2Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, CA
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  • ORCID record for Cristina M. Alvira
  • For correspondence: calvira@stanford.edu
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Abstract

At birth, the lungs experience a sudden transition from a pathogen-free, hypoxic, fluid-filled environment to a pathogen-rich, rhythmically distended air-liquid interface. While many studies focus on adult tissue, the heterogeneity of immune cells in the perinatal lung remains unexplored. Here, we combine single cell transcriptomics with in situ hybridization to present an atlas of the murine lung immune compartment from E18.5 to P21, a critical period of lung development. We show that the late embryonic lung is dominated by specialized proliferative macrophages with a surprising physical interaction with the developing vasculature. These macrophages disappear after birth and are replaced by a complex and dynamic mixture of macrophage subtypes, dendritic cells, granulocytes, and lymphocytes. Detailed characterization of macrophage diversity revealed five distinct subpopulations, with both unique gene expression signatures and developmental gradients and localizing specifically to the lung parenchyma, vessels and airways, suggesting distinct physiological functions in tissue remodeling, angiogenesis, and immunity. Three dendritic cell populations, basophils, mast cells and neutrophils appear poised for rapid immune response. In contrast, although lymphocytes increased in abundance during early postnatal life, they remained functionally immature. These data identify a marked increase in lung cell immune diversity concomitant with the transition from fetal to air-breathing life, with precise orchestration of unique macrophage subpopulations across postnatal development to fill context-specific structural and immunomodulatory functions. These data both broaden the putative roles for immune cells in the developing lung and provide a framework for understanding how external insults alter lung immune cell phenotype during a period of rapid growth and heightened vulnerability.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted February 11, 2020.
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Form and function: diverse homeostatic and immunomodulatory roles of immune cells in the developing lung revealed at single cell resolution
Racquel Domingo-Gonzalez, Fabio Zanini, Xibing Che, Min Liu, Robert C. Jones, Michael A. Swift, Stephen R. Quake, David N. Cornfield, Cristina M. Alvira
bioRxiv 2020.02.10.942359; doi: https://doi.org/10.1101/2020.02.10.942359
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Form and function: diverse homeostatic and immunomodulatory roles of immune cells in the developing lung revealed at single cell resolution
Racquel Domingo-Gonzalez, Fabio Zanini, Xibing Che, Min Liu, Robert C. Jones, Michael A. Swift, Stephen R. Quake, David N. Cornfield, Cristina M. Alvira
bioRxiv 2020.02.10.942359; doi: https://doi.org/10.1101/2020.02.10.942359

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