Although single-cell RNA sequencing studies have begun to provide compendia of cell expression profiles1-9, it has been difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here, using droplet- and plate-based single-cell RNA sequencing of approximately 75,000 human cells across all lung tissue compartments and circulating blood, combined with a multi-pronged cell annotation approach, we create an extensive cell atlas of the human lung. We define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 out of 45 previously known cell types and 14 previously unknown ones. This comprehensive molecular atlas identifies the biochemical functions of lung cells and the transcription factors and markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signalling interactions and immune cell homing; and identifies cell types that are directly affected by lung disease genes and respiratory viruses. By comparing human and mouse data, we identified 17 molecular cell types that have been gained or lost during lung evolution and others with substantially altered expression profiles, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions and interactions are achieved in development and tissue engineering and altered in disease and evolution.

中文翻译：

---

基于单细胞 RNA 测序的人肺分子细胞图谱

尽管单细胞 RNA 测序研究已开始提供细胞表达谱 1-9 的概要，但系统地识别和定位单个器官中的所有分子细胞类型以创建完整的分子细胞图谱仍然很困难。在这里，我们使用基于液滴和平板的单细胞 RNA 测序技术，对所有肺组织区室和循环血液中的约 75,000 个人类细胞进行测序，并结合多管齐下的细胞注释方法，创建了广泛的人类肺部细胞图谱。我们定义了人肺中 58 个细胞群的基因表达谱和解剖位置，包括 45 种先前已知的细胞类型中的 41 种和 14 种先前未知的细胞类型。该综合分子图谱确定了肺细胞的生化功能以及用于制造和监测它们的转录因子和标记物；定义循环激素的细胞靶标并预测局部信号相互作用和免疫细胞归巢；并识别直接受肺部疾病基因和呼吸道病毒影响的细胞类型。通过比较人类和小鼠的数据，我们鉴定了在肺进化过程中获得或丢失的 17 种分子细胞类型，以及其他表达谱发生显着改变的分子细胞类型，揭示了器官进化过程中细胞类型和细胞类型特异性基因表达的广泛可塑性，包括表达开关细胞类型之间。该图谱为研究肺细胞特性、功能和相互作用如何在发育和组织工程中实现以及如何在疾病和进化中改变提供了分子基础。