Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry

Summary: We have performed an in-depth single-cell phenotypic characterization of high-grade serous ovarian cancer (HGSOC) by multiparametric mass cytometry (CyTOF). Using a CyTOF antibody panel to interrogate features of HGSOC biology, combined with unsupervised computational analysis, we identifie...

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Main Authors: Veronica D. Gonzalez, Nikolay Samusik, Tiffany J. Chen, Erica S. Savig, Nima Aghaeepour, David A. Quigley, Ying-Wen Huang, Valeria Giangarrà, Alexander D. Borowsky, Neil E. Hubbard, Shih-Yu Chen, Guojun Han, Alan Ashworth, Thomas J. Kipps, Jonathan S. Berek, Garry P. Nolan, Wendy J. Fantl
Format: Article
Language:English
Published: Elsevier 2018-02-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124718301025
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author Veronica D. Gonzalez
Nikolay Samusik
Tiffany J. Chen
Erica S. Savig
Nima Aghaeepour
David A. Quigley
Ying-Wen Huang
Valeria Giangarrà
Alexander D. Borowsky
Neil E. Hubbard
Shih-Yu Chen
Guojun Han
Alan Ashworth
Thomas J. Kipps
Jonathan S. Berek
Garry P. Nolan
Wendy J. Fantl
spellingShingle Veronica D. Gonzalez
Nikolay Samusik
Tiffany J. Chen
Erica S. Savig
Nima Aghaeepour
David A. Quigley
Ying-Wen Huang
Valeria Giangarrà
Alexander D. Borowsky
Neil E. Hubbard
Shih-Yu Chen
Guojun Han
Alan Ashworth
Thomas J. Kipps
Jonathan S. Berek
Garry P. Nolan
Wendy J. Fantl
Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry
Cell Reports
high grade serious ovarian cancer
single cell
mass cytometry
CyTOF
hierarchical clustering
phenotypic characterization
author_facet Veronica D. Gonzalez
Nikolay Samusik
Tiffany J. Chen
Erica S. Savig
Nima Aghaeepour
David A. Quigley
Ying-Wen Huang
Valeria Giangarrà
Alexander D. Borowsky
Neil E. Hubbard
Shih-Yu Chen
Guojun Han
Alan Ashworth
Thomas J. Kipps
Jonathan S. Berek
Garry P. Nolan
Wendy J. Fantl
author_sort Veronica D. Gonzalez
title Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry
title_short Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry
title_full Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry
title_fullStr Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry
title_full_unstemmed Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry
title_sort commonly occurring cell subsets in high-grade serous ovarian tumors identified by single-cell mass cytometry
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2018-02-01
description Summary: We have performed an in-depth single-cell phenotypic characterization of high-grade serous ovarian cancer (HGSOC) by multiparametric mass cytometry (CyTOF). Using a CyTOF antibody panel to interrogate features of HGSOC biology, combined with unsupervised computational analysis, we identified noteworthy cell types co-occurring across the tumors. In addition to a dominant cell subset, each tumor harbored rarer cell phenotypes. One such group co-expressed E-cadherin and vimentin (EV), suggesting their potential role in epithelial mesenchymal transition, which was substantiated by pairwise correlation analyses. Furthermore, tumors from patients with poorer outcome had an increased frequency of another rare cell type that co-expressed vimentin, HE4, and cMyc. These poorer-outcome tumors also populated more cell phenotypes, as quantified by Simpson’s diversity index. Thus, despite the recognized genomic complexity of the disease, the specific cell phenotypes uncovered here offer a focus for therapeutic intervention and disease monitoring.
topic high grade serious ovarian cancer
single cell
mass cytometry
CyTOF
hierarchical clustering
phenotypic characterization
url http://www.sciencedirect.com/science/article/pii/S2211124718301025
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spelling doaj-c6d07ffaf8194872a0ab6903a46f592e2020-11-25T03:37:32ZengElsevierCell Reports2211-12472018-02-012271875188810.1016/j.celrep.2018.01.053Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass CytometryVeronica D. Gonzalez0Nikolay Samusik1Tiffany J. Chen2Erica S. Savig3Nima Aghaeepour4David A. Quigley5Ying-Wen Huang6Valeria Giangarrà7Alexander D. Borowsky8Neil E. Hubbard9Shih-Yu Chen10Guojun Han11Alan Ashworth12Thomas J. Kipps13Jonathan S. Berek14Garry P. Nolan15Wendy J. Fantl16Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USABaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USABaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USABaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USABaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USAHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 Third Street, San Francisco, CA 94158, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, 1450 Third Street, San Francisco, CA 94158, USABaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USABaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USACenter for Comparative Medicine, University of California, Davis, Davis, CA 95616, USA; Department of Pathology and Laboratory Medicine, Comprehensive Cancer Center, University of California, Davis School of Medicine, Sacramento, CA 95817, USACenter for Comparative Medicine, University of California, Davis, Davis, CA 95616, USA; Department of Pathology and Laboratory Medicine, Comprehensive Cancer Center, University of California, Davis School of Medicine, Sacramento, CA 95817, USABaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USABaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USAHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 Third Street, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, 1450 Third Street, San Francisco, CA 94158, USAMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USAStanford Comprehensive Cancer Institute and Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USABaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USAStanford Comprehensive Cancer Institute and Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA; Corresponding authorSummary: We have performed an in-depth single-cell phenotypic characterization of high-grade serous ovarian cancer (HGSOC) by multiparametric mass cytometry (CyTOF). Using a CyTOF antibody panel to interrogate features of HGSOC biology, combined with unsupervised computational analysis, we identified noteworthy cell types co-occurring across the tumors. In addition to a dominant cell subset, each tumor harbored rarer cell phenotypes. One such group co-expressed E-cadherin and vimentin (EV), suggesting their potential role in epithelial mesenchymal transition, which was substantiated by pairwise correlation analyses. Furthermore, tumors from patients with poorer outcome had an increased frequency of another rare cell type that co-expressed vimentin, HE4, and cMyc. These poorer-outcome tumors also populated more cell phenotypes, as quantified by Simpson’s diversity index. Thus, despite the recognized genomic complexity of the disease, the specific cell phenotypes uncovered here offer a focus for therapeutic intervention and disease monitoring.http://www.sciencedirect.com/science/article/pii/S2211124718301025high grade serious ovarian cancersingle cellmass cytometryCyTOFhierarchical clusteringphenotypic characterization