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

Abstract

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.

Developmental diversity and unique sensitivity to injury of lung endothelial subtypes during a period of rapid postnatal growth

“…1A). After optimizing lung dissociation to maximize EC viability and yield 14 , we perfused the pulmonary circulation, digested the lungs and performed fluorescent activated cell sorting (FACS) to select CD31+ EC. We transcriptionally profiled 2931 EC from 10 C57BL/6 mouse lungs using plate-based scRNASeq, at a depth of approximately 1 million reads per cell.…”

“…However, current knowledge about the molecular regulation of pulmonary angiogenesis is largely based upon studies performed on whole lung, which is limited by ensemble averaging, or extensively passaged primary cells. Single cell transcriptomics has provided a high-resolution picture of the adult lung in mice 10 and humans 11 and begun to shed light on specific populations in the epithelial 12 and immune compartments 13,14 . However, the distinct EC subtypes composing the immature lung vasculature and their spatial locations, and physiological roles have not been fully characterized.…”

Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study

“…Since gene expression is regulated both at the transcriptional and epigenomic levels, the unprecedented power of carrying out concomitant and integrated analyses of scRNA-seq and scATAC-seq data are increasingly evident. These new powerful tools have revealed the heterogeneity of cell types in the liver ( Zhao et al, 2020 ), lungs ( Domingo-Gonzalez et al, 2020 ), heart ( Bykov et al, 2020 ), immune cells ( Villani et al, 2017 ), and ECs ( Kalluri et al, 2019 ; Kalucka et al, 2020 ) under various physiological and pathological conditions.…”

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

“…Lung development initiates in utero and continues until infancy, and involves a complex process regulated by different types of cells, factors and mediators, such as macrophages, dendritic cells and lymphocytes (1). Abnormal lung development can be harmful to respiratory health, which may result in bronchopulmonary dysplasia, neonatal respiratory distress syndrome, asthma and chronic obstructive emphysema (2)(3)(4).…”