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

First Author  Cohen M Year  2018
Journal  Cell Volume  175
Issue  4 Pages  1031-1044.e18
PubMed ID  30318149 Mgi Jnum  J:268638
Mgi Id  MGI:6259389 Doi  10.1016/j.cell.2018.09.009
Citation  Cohen M, et al. (2018) Lung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting. Cell 175(4):1031-1044.e18
abstractText  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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