Journal
CELL
Volume 175, Issue 4, Pages 1031-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2018.09.009
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Funding
- Chan Zuckerberg Initiative (CZI)
- HHMI International Scholar award
- European Research Council Consolidator Grant (ERC-COG) [724471-HemTree2.0]
- MRA Established Investigator Award [509044]
- Israel Science Foundation [703/15]
- Helen and Martin Kimmel Award for Innovative Investigation
- SCA award of the Wolfson Foundation
- Wolfson Foundation
- Austrian Science Fund (FWF), DK Cell Communication in Health and Disease [W 1205-B09]
- Special Research Program Chromatin Landscapes [L-Mac: F 6104-B21]
- postdoctoral fellowship in Applied and Engineering Science, Israeli Government, Ministry of Science and Technology
- Clore fellowship
- EMBO short-term fellowship [6879]
- Family Charitable Trust
- [ERC-2015-AdG-695136]
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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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