肺部健康与疾病的细胞整合图谱
An integrated cell atlas of the lung in health and disease.
机构信息
Department of Computational Health, Institute of Computational Biology, Helmholtz Center Munich, Munich, Germany.
TUM School of Life Sciences, Technical University of Munich, Munich, Germany.
出版信息
Nat Med. 2023 Jun;29(6):1563-1577. doi: 10.1038/s41591-023-02327-2. Epub 2023 Jun 8.
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
单细胞技术改变了我们对人体组织的理解。然而,研究通常只捕获有限数量的供体,并且对细胞类型的定义存在分歧。整合多个单细胞数据集可以解决这些单个研究的局限性,并捕获人群中的可变性。在这里,我们展示了整合的人类肺部细胞图谱(HLCA),将 49 个人类呼吸系统数据集整合到一个图谱中,其中包含了来自 486 个人的超过 240 万个细胞。HLCA 提供了具有匹配标记基因的共识细胞类型重新注释,包括稀有和以前未描述的细胞类型的注释。利用 HLCA 中个体的数量和多样性,我们确定了与年龄、性别和体重指数等人口统计学协变量相关的基因模块,以及沿着支气管树的近-远轴表达变化的基因模块。将新数据映射到 HLCA 上可以实现快速的数据注释和解释。使用 HLCA 作为研究疾病的参考,我们在多个肺部疾病中识别出共享的细胞状态,包括 COVID-19、肺纤维化和肺癌中的 SPP1 致纤维化单核细胞衍生的巨噬细胞。总体而言,HLCA 为人类细胞图谱内的大规模、跨数据集器官图谱的开发和使用提供了一个范例。