Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung revealed at single cell resolution

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 during 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 a precise orchestration of five 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.

File formats:

- tsv (gzipped): separate files for gene expression counts and cell metadata

- loom: single file with both cell metadata and gene expression counts

Metadata columns (tab-separated):

- the first column is cell id

- title: same as cell id

- source name: distal lung

- organism: Mus musculus

- Sequencing run: DC20, DC21, DC23, DC25, DC30, DC35, DC36

- Gender: F or M

- Plate: 1 or 2 (the number of 384 well plate the cell for sorted into)

- Well: A1-P24 (the well number within the 384 well plate the cell was sorted into)

- Timepoint: E18.5, P1, P7, or P21

- Cell Type: immune

- Cell Subtype: one of several subtypes

- Mousename: mouse id
- Coverage: number of read pairs uniquely mapped to the mouse genome

- Number of genes: number of genes detected with 1+ reads

- tsne_1: t-SNE coordinate 1

- tsne_2: t-SNE coordinate 2

- molecule: mRNA
- description: none

- processed data file: none

- raw file 1: fastq file for read 1 (on GEO: GSE147668)

- raw file 2: fastq file for read 2 (on GEO: GSE147668)