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体外多细胞培养系统的单细胞图谱揭示了人类肺部的体内谱系轨迹和细胞状态。

A single-cell atlas of in vitro multiculture systems uncovers the in vivo lineage trajectory and cell state in the human lung.

机构信息

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.

Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

出版信息

Exp Mol Med. 2023 Aug;55(8):1831-1842. doi: 10.1038/s12276-023-01076-z. Epub 2023 Aug 15.

DOI:10.1038/s12276-023-01076-z
PMID:37582976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10474282/
Abstract

We present an in-depth single-cell atlas of in vitro multiculture systems on human primary airway epithelium derived from normal and diseased lungs of 27 individual donors. Our large-scale single-cell profiling identified new cell states and differentiation trajectories of rare airway epithelial cell types in human distal lungs. By integrating single-cell datasets of human lung tissues, we discovered immune-primed subsets enriched in lungs and organoids derived from patients with chronic respiratory disease. To demonstrate the full potential of our platform, we further illustrate transcriptomic responses to various respiratory virus infections in vitro airway models. Our work constitutes a single-cell roadmap for the cellular and molecular characteristics of human primary lung cells in vitro and their relevance to human tissues in vivo.

摘要

我们呈现了一份深入的单细胞图谱,展示了来自 27 位个体供体的正常和患病肺部的体外多培养系统中的人类初级气道上皮细胞。我们的大规模单细胞分析鉴定了人类远端肺部中罕见气道上皮细胞类型的新细胞状态和分化轨迹。通过整合人类肺部组织的单细胞数据集,我们发现了在慢性呼吸道疾病患者的肺部和类器官中富集的免疫激活亚群。为了展示我们平台的全部潜力,我们进一步说明了体外气道模型中各种呼吸道病毒感染的转录组反应。我们的工作为人类初级肺细胞在体外的细胞和分子特征以及它们与体内人类组织的相关性提供了单细胞路线图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/5a359d74922c/12276_2023_1076_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/57ad983769a3/12276_2023_1076_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/cf655781ca94/12276_2023_1076_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/4252106124f5/12276_2023_1076_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/9e8b3e7610e9/12276_2023_1076_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/5a359d74922c/12276_2023_1076_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/57ad983769a3/12276_2023_1076_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/cf655781ca94/12276_2023_1076_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/4252106124f5/12276_2023_1076_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/9e8b3e7610e9/12276_2023_1076_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fa/10474282/5a359d74922c/12276_2023_1076_Fig5_HTML.jpg

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