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

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....

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Bibliographic Details
Published in:Cell Vol. 175; no. 4; p. 1031
Main Authors: Cohen, Merav, Giladi, Amir, Gorki, Anna-Dorothea, Solodkin, Dikla Gelbard, Zada, Mor, Hladik, Anastasiya, Miklosi, Andras, Salame, Tomer-Meir, Halpern, Keren Bahar, David, Eyal, Itzkovitz, Shalev, Harkany, Tibor, Knapp, Sylvia, Amit, Ido
Format: Journal Article
Language:English
Published: United States 01.11.2018
Subjects:
lung
single-cell RNA sequencing
development
signaling
alveolar macrophages
immune system
basophils
cellular interaction
ISSN:1097-4172, 1097-4172
Online Access:Get more information
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Summary: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.
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2018.09.009