Lung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting

Cell. 2018 Nov 1;175(4):1031-1044.e18. doi: 10.1016/j.cell.2018.09.009. Epub 2018 Oct 11.


Lung development and function arises from the interactions between diverse cell types and lineages. Using single-cell RNA sequencing (RNA-seq), we characterize the cellular composition of the lung during development and identify vast dynamics in cell composition and their molecular characteristics. Analyzing 818 ligand-receptor interaction pairs within and between cell lineages, we identify broadly interacting cells, including AT2, innate lymphocytes (ILCs), and basophils. Using interleukin (IL)-33 receptor knockout mice and in vitro experiments, we show that basophils establish a lung-specific function imprinted by IL-33 and granulocyte-macrophage colony-stimulating factor (GM-CSF), characterized by unique signaling of cytokines and growth factors important for stromal, epithelial, and myeloid cell fates. Antibody-depletion strategies, diphtheria toxin-mediated selective depletion of basophils, and co-culture studies show that lung resident basophils are important regulators of alveolar macrophage development and function. Together, our study demonstrates how whole-tissue signaling interaction map on the single-cell level can broaden our understanding of cellular networks in health and disease.

Keywords: alveolar macrophages; basophils; cellular interaction; development; immune system; lung; signaling; single-cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basophils / metabolism*
  • Cell Communication*
  • Cell Differentiation
  • Cell Line, Tumor
  • Cells, Cultured
  • Female
  • Genomic Imprinting*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Interleukin-33 / metabolism
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction
  • Single-Cell Analysis
  • Transcriptome*


  • Interleukin-33
  • Granulocyte-Macrophage Colony-Stimulating Factor