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.

中文翻译：

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肺单细胞信号相互作用图揭示了嗜碱性粒细胞在巨噬细胞印迹中的作用。

肺的发育和功能源于多种细胞类型和谱系之间的相互作用。使用单细胞RNA测序（RNA-seq），我们可以表征发育过程中肺的细胞组成，并确定细胞组成及其分子特征的巨大动态。分析细胞系内和细胞系之间的818个配体-受体相互作用对，我们确定了广泛相互作用的细胞，包括AT2，先天淋巴细胞（ILC）和嗜碱性粒细胞。使用白介素（IL）-33受体敲除小鼠和体外实验，我们表明嗜碱性粒细胞建立了由IL-33和粒细胞-巨噬细胞集落刺激因子（GM-CSF）印记的肺特异性功能，其特征在于细胞因子的独特信号传导和对基质，上皮和髓样细胞命运重要的生长因子。抗体耗竭策略，白喉毒素介导的嗜碱性粒细胞的选择性耗竭，共培养研究表明，肺部驻留的嗜碱性粒细胞是肺泡巨噬细胞发育和功能的重要调节剂。总之，我们的研究证明了单细胞水平上的全组织信号传导相互作用图谱可如何拓宽我们对健康和疾病中细胞网络的理解。