Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma

被引：566

作者：

Ji, Andrew L. ^{[1
,2
]}

Rubin, Adam J. ^{[1
]}

Thrane, Kim ^{[3
]}

Jiang, Sizun ^{[4
]}

Reynolds, David L. ^{[1
]}

Meyers, Robin M. ^{[1
]}

Guo, Margaret G. ^{[1
]}

George, Benson M. ^{[5
]}

Mollbrink, Annelie ^{[3
]}

Bergenstrahle, Joseph ^{[3
]}

Larsson, Ludvig ^{[3
]}

Bai, Yunhao ^{[4
]}

Zhu, Bokai ^{[4
]}

Bhaduri, Aparna ^{[6
]}

Meyers, Jordan M. ^{[1
]}

Rovira-Clave, Xavier ^{[4
]}

Hollmig, S. Tyler ^{[1
]}

Aasi, Sumaira Z. ^{[1
]}

Nolan, Garry P. ^{[4
]}

Lundeberg, Joakim ^{[3
]}

Khavari, Paul A. ^{[1
,2
,7
]}

机构：

[1] Stanford Univ, Program Epithelial Biol, Sch Med, Stanford, CA 94305 USA

[2] Stanford Univ, Stanford Canc Inst, Sch Med, Stanford, CA 94305 USA

[3] KTH Royal Inst Technol, Dept Gene Technol, Sci Life Lab, Tomtebodavagen 23, S-17165 Solna, Sweden

[4] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA

[5] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA

[6] Univ Calif San Francisco UCSF, Dept Neurol, San Francisco, CA 94122 USA

[7] Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA 94304 USA

来源：

CELL | 2020年 / 182卷 / 02期

基金：

瑞典研究理事会; 美国国家卫生研究院; 芬兰科学院;

关键词：

BREAST-CANCER; GENE-EXPRESSION; HAIR FOLLICLE; BETA; MICROENVIRONMENT; HETEROGENEITY; VISUALIZATION; METASTASIS; MECHANISMS; MUTATIONS;

D O I：

10.1016/j.cell.2020.05.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.

引用

页码：497 / +

页数：40

共 100 条

[1]

Aibar S, 2017, NAT METHODS, V14, P1083, DOI [10.1038/NMETH.4463, 10.1038/nmeth.4463]

[2] EMT: 2016 [J].

Angela Nieto, M. ;

Huang, Ruby Yun-Ju ;

Jackson, Rebecca A. ;

Thiery, Jean Paul .

CELL, 2016, 166 (01) :21-45

[3] Multiplexed ion beam imaging of human breast tumors [J].

Angelo, Michael ;

Bendall, Sean C. ;

Finck, Rachel ;

Hale, Matthew B. ;

Hitzman, Chuck ;

Borowsky, Alexander D. ;

Levenson, Richard M. ;

Lowe, John B. ;

Liu, Scot D. ;

Zhao, Shuchun ;

Natkunam, Yasodha ;

Nolan, Garry P. .

NATURE MEDICINE, 2014, 20 (04) :436-+

[4] Opposing Functions of Interferon Coordinate Adaptive and Innate Immune Responses to Cancer Immune Checkpoint Blockade [J].

Benci, Joseph L. ;

Johnson, Lexus R. ;

Choa, Ruth ;

Xu, Yuanming ;

Qiu, Jingya ;

Zhou, Zilu ;

Xu, Bihui ;

Ye, Darwin ;

Nathanson, Katherine L. ;

June, Carl H. ;

Wherry, E. John ;

Zhang, Nancy R. ;

Ishwaran, Hemant ;

Hellmann, Matthew D. ;

Wolchok, Jedd D. ;

Kambayashi, Taku ;

Minn, Andy J. .

CELL, 2019, 178 (04) :933-+

[5] Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards [J].

Bronte, Vincenzo ;

Brandau, Sven ;

Chen, Shu-Hsia ;

Colombo, Mario P. ;

Frey, Alan B. ;

Greten, Tim F. ;

Mandruzzato, Susanna ;

Murray, Peter J. ;

Ochoa, Augusto ;

Ostrand-Rosenberg, Suzanne ;

Rodriguez, Paulo C. ;

Sica, Antonio ;

Umansky, Viktor ;

Vonderheide, Robert H. ;

Gabrilovich, Dmitry I. .

NATURE COMMUNICATIONS, 2016, 7

[6]

Browaeys R, 2019, NAT METHODS, V17, P159, DOI [10.1101/820936, DOI 10.1101/820936]

[7] Integrating single-cell transcriptomic data across different conditions, technologies, and species [J].

Butler, Andrew ;

Hoffman, Paul ;

Smibert, Peter ;

Papalexi, Efthymia ;

Satija, Rahul .

NATURE BIOTECHNOLOGY, 2018, 36 (05) :411-+

[8] Talins and kindlins: partners in integrin-mediated adhesion [J].

Calderwood, David A. ;

Campbell, Iain D. ;

Critchley, David R. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2013, 14 (08) :503-517

[9] Phenotypical and functional specialization of FOXP3+ regulatory T cells [J].

Campbell, Daniel J. ;

Koch, Meghan A. .

NATURE REVIEWS IMMUNOLOGY, 2011, 11 (02) :119-130

[10] Molecular mechanisms of T cell co-stimulation and co-inhibition [J].

Chen, Lieping ;

Flies, Dallas B. .

NATURE REVIEWS IMMUNOLOGY, 2013, 13 (04) :227-242

← 1 2 3 4 5 6 7 8 9 10 →