Resolving the Spatial and Cellular Architecture of Lung Adenocarcinoma by Multiregion Single-Cell Sequencing
Autor: | Guangchun Han, Warapen Treekitkarnmongkol, Ansam Sinjab, Tina Cascone, Jichao Chen, Humam Kadara, Ignacio I. Wistuba, Christopher S. Stevenson, Paul Scheet, Edwin R. Parra, Patrick M. Brennan, Luisa M. Solis, Carmen Behrens, Daniel G. Rosen, Jianjun Zhang, Danielle R. Little, Dapeng Hao, Beatriz Sanchez-Espiridion, Ruiping Wang, Linh M. Tran, Kostyantyn Krysan, Junya Fujimoto, John V. Heymach, Seyed Javad Moghaddam, Kieko Hara, Samer Bazzi, Minghao Dang, Avrum Spira, Kyle Chang, Dzifa Y. Duose, Don L. Gibbons, Boris Sepesi, Steven M. Dubinett, Linghua Wang, Elena Bogatenkova, Edwin J. Ostrin, Maria Gabriela Raso, Lauren Averett Byers, Jiexin Zhang, Hitoshi Dejima, Enyu Dai, Junya Fukuoka |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Lung Neoplasms Cell Adenocarcinoma of Lung Computational biology CD8-Positive T-Lymphocytes Biology medicine.disease_cause Interactome Article Transcriptome 03 medical and health sciences 0302 clinical medicine Tumor Microenvironment medicine Humans Cytotoxic T cell CD24 medicine.disease Phenotype 030104 developmental biology medicine.anatomical_structure Oncology Single cell sequencing 030220 oncology & carcinogenesis Adenocarcinoma KRAS Single-Cell Analysis CD8 |
Zdroj: | Cancer Discov |
ISSN: | 2159-8290 2159-8274 |
Popis: | Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from five early-stage LUADs and 14 multiregion normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to LUADs. LUADs also exhibit pronounced intratumor cell heterogeneity within single sites and transcriptional lineage-plasticity programs. T regulatory cell phenotypes are increased in normal tissues with proximity to LUAD, in contrast to diminished signatures and fractions of cytotoxic CD8+ T cells, antigen-presenting macrophages, and inflammatory dendritic cells. We further find that the LUAD ligand–receptor interactome harbors increased expression of epithelial CD24, which mediates protumor phenotypes. These data provide a spatial atlas of LUAD evolution, and a resource for identification of targets for its treatment. Significance: The geospatial ecosystem of the peripheral lung and early-stage LUAD is not known. Our multiregion single-cell sequencing analyses unravel cell populations, states, and phenotypes in the spatial and ecologic evolution of LUAD from the lung that comprise high-potential targets for early interception. This article is highlighted in the In This Issue feature, p. 2355 |
Databáze: | OpenAIRE |
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