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

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

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
2
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, 1090 Vienna, Austria.
3
Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria.
4
Flow Cytometry Unit, Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel.
5
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
6
Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria; Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden.
7
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: ido.amit@weizmann.ac.il.

Abstract

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

PMID:
30318149
DOI:
10.1016/j.cell.2018.09.009

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