Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution
At birth, the lungs rapidly transition from a pathogen-free, hypoxic environment to a pathogen-rich, rhythmically distended air-liquid interface. Although many studies have focused on the adult lung, the perinatal lung remains unexplored. Here, we present an atlas of the murine lung immune compartment during early postnatal 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 dynamic mixture of macrophage subtypes, dendritic cells, granulocytes, and lymphocytes. Detailed characterization of macrophage diversity revealed an orchestration of distinct subpopulations across postnatal development to fill context-specific functions in tissue remodeling, angiogenesis, and immunity. These data both broaden the putative roles for immune cells in the developing lung and provide a framework for understanding how external insults alter immune cell phenotype during a period of rapid lung growth and heightened vulnerability.
Sequencing data have been deposited in GEO under accession code GSE147668. Gene count and metadata tables are also available on FigShare at https://figshare.com/articles/Diverse_homeostatic_and_immunomodulatory _roles_of_immune_cells_in_the_developing_mouse_lung_revealed_at_single_cell_resolution/12043365
scRNA-seq analysis of lung CD64-expressing mononuclear cells, patrolling and classical monocytes from steady-state C57BL/6J miceEBI/EMBL ArrayExpress; 10.1038/s41467-019-11843-0.
Tabula Muris: Transcriptomic characterization of 20 organs and tissues from Mus musculus at single cell resolution: Single-cell RNA-seq data from Smart-seq2 sequencing of FACS sorted cells (v2)FigShare; 10.1038/s41586-018-0590-4.
Article and author information
National Institutes of Health (HL122918)
- Cristina M Alvira
National Institutes of Health (HD092316)
- David N Cornfield
- Cristina M Alvira
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#19087) of Stanford University School of Medicine.
- Emma L Rawlins, University of Cambridge, United Kingdom
- Received: March 13, 2020
- Accepted: May 13, 2020
- Accepted Manuscript published: June 2, 2020 (version 1)
- Version of Record published: July 13, 2020 (version 2)
© 2020, Domingo-Gonzalez et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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