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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Veröffentlicht in:	Cell Jg. 175; H. 4; S. 1031
Hauptverfasser:	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
Sprache:	Englisch
Veröffentlicht:	United States 01.11.2018
Schlagworte:	lung single-cell RNA sequencing development signaling alveolar macrophages immune system basophils cellular interaction
ISSN:	1097-4172, 1097-4172
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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.
AbstractList	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.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. 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.
Author	Miklosi, Andras Solodkin, Dikla Gelbard Harkany, Tibor David, Eyal Itzkovitz, Shalev Salame, Tomer-Meir Zada, Mor Cohen, Merav Knapp, Sylvia Giladi, Amir Amit, Ido Hladik, Anastasiya Halpern, Keren Bahar Gorki, Anna-Dorothea
Author_xml	– sequence: 1 givenname: Merav surname: Cohen fullname: Cohen, Merav organization: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel – sequence: 2 givenname: Amir surname: Giladi fullname: Giladi, Amir organization: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel – sequence: 3 givenname: Anna-Dorothea surname: Gorki fullname: Gorki, Anna-Dorothea organization: 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 – sequence: 4 givenname: Dikla Gelbard surname: Solodkin fullname: Solodkin, Dikla Gelbard organization: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel – sequence: 5 givenname: Mor surname: Zada fullname: Zada, Mor organization: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel – sequence: 6 givenname: Anastasiya surname: Hladik fullname: Hladik, Anastasiya organization: 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 – sequence: 7 givenname: Andras surname: Miklosi fullname: Miklosi, Andras organization: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria – sequence: 8 givenname: Tomer-Meir surname: Salame fullname: Salame, Tomer-Meir organization: Flow Cytometry Unit, Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel – sequence: 9 givenname: Keren Bahar surname: Halpern fullname: Halpern, Keren Bahar organization: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel – sequence: 10 givenname: Eyal surname: David fullname: David, Eyal organization: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel – sequence: 11 givenname: Shalev surname: Itzkovitz fullname: Itzkovitz, Shalev organization: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel – sequence: 12 givenname: Tibor surname: Harkany fullname: Harkany, Tibor organization: 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 – sequence: 13 givenname: Sylvia surname: Knapp fullname: Knapp, Sylvia organization: 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 – sequence: 14 givenname: Ido surname: Amit fullname: Amit, Ido email: ido.amit@weizmann.ac.il organization: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: ido.amit@weizmann.ac.il
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/30318149$$D View this record in MEDLINE/PubMed
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Copyright	Copyright © 2018 Elsevier Inc. All rights reserved.
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Keywords	lung single-cell RNA sequencing development signaling alveolar macrophages immune system basophils cellular interaction
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References	30388447 - Cell. 2018 Nov 1;175(4):898-900
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Snippet	Lung development and function arises from the interactions between diverse cell types and lineages. Using single-cell RNA sequencing (RNA-seq), we characterize...
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Title	Lung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting
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