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PMID: 29079795 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Comprehensive single-cell transcriptome analysis reveals heterogeneity in endometrioid adenocarcinoma tissues.

Scientific reports ·Vol. 7 ·No. 1 ·2017-00-27 ·Pages 14225

Hashimoto S, Tabuchi Y, Yurino H, Hirohashi Y, Deshimaru S, Asano T, Mariya T, Oshima K, Takamura Y, Ukita Y, Ametani A, Kondo N, Monma N, Takeda T, Misu S, Okayama T, Ikeo K, Saito T, Kaneko S, Suzuki Y, Hattori M, Matsushima K, Torigoe T

Abstract

Single cell transcriptome analysis of a cancer tissue can provide objective assessment of subtype population or the activation of each of various microenvironment component cells. In this study, we applied our newly developed technique of single cell analysis to the myometrial infiltration side (M-side) and the endometrial side (E-side) of a human endometrioid adenocarcinoma with squamous differentiation tissues. We also analyzed spherogenic cultures derived from the same tissue to identify putative regulators of stemness in vivo. Cancer cells in the E-side were highly malignant compared with those in the M-side. Many cells on the E-side were positive for spheroid-specific tumorigenesis-related markers including SOX2. In addition, there were higher numbers of epithelial-to-mesenchymal transition (EMT) cells in the E-side compared with the M-side. This study identified a site containing cells with high malignant potential such as EMT and cancer stem-like cells in cancer tissues. Finally, we demonstrate that established endometrioid adenocarcinoma subtype classifiers were variably expressed across individual cells within a tumor. Thus, such intratumoral heterogeneity may be related to prognostic implications.

MeSH Terms
Adenocarcinoma/diagnosis,genetics,immunology,pathology Adult Chemokines/genetics Endometrial Neoplasms/diagnosis,genetics,immunology,pathology Female Gene Expression Profiling Humans Middle Aged Neoplasm Staging Prognosis Single-Cell Analysis Spheroids, Cellular/pathology
Chemicals
Chemokines
Authors & Affiliations
23 authors, click to expand affiliations / ORCID
Hashimoto Shinichi
Department of Integrative Medicine for Longevity, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, 920-8641, Japan. hashimoto@med.kanazawa-u.ac.jp. | CREST, Japan Science and Technology Agency, Tokyo, 102-0076, Japan. hashimoto@med.kanazawa-u.ac.jp.
Tabuchi Yuta
Department of Pathology, School of Medicine, Sapporo Medical University, Hokkaido, 060-0061, Japan.
Yurino Hideaki
Department of Integrative Medicine for Longevity, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, 920-8641, Japan. | CREST, Japan Science and Technology Agency, Tokyo, 102-0076, Japan.
Hirohashi Yoshihiko
CREST, Japan Science and Technology Agency, Tokyo, 102-0076, Japan. | Department of Pathology, School of Medicine, Sapporo Medical University, Hokkaido, 060-0061, Japan.
Deshimaru Shungo
Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
Asano Takuya
Department of Pathology, School of Medicine, Sapporo Medical University, Hokkaido, 060-0061, Japan.
Mariya Tasuku
Department of Pathology, School of Medicine, Sapporo Medical University, Hokkaido, 060-0061, Japan.
Oshima Kenshiro
Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, 277-8561, Japan.
Takamura Yuzuru
Department of Bioscience and Biotechnology, Japan Advanced Institute of Science and Technology, Ishikawa, 923-1292, Japan.
Ukita Yoshiaki
Faculty of Engineering, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, Yamanashi, 400-8511, Japan.
Ametani Akio
Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
Kondo Naoto
RIKEN Center for Life Science Technologies, Kanagawa, 230-0045, Japan.
Monma Norikazu
Laboratory of DNA Data Analysis, National Institute of Genetics, Shizuoka, 411-8540, Japan.
Takeda Tadayuki
RIKEN Center for Life Science Technologies, Kanagawa, 230-0045, Japan.
Misu Sadahiko
Laboratory of DNA Data Analysis, National Institute of Genetics, Shizuoka, 411-8540, Japan.
Okayama Toshitugu
Laboratory of DNA Data Analysis, National Institute of Genetics, Shizuoka, 411-8540, Japan.
Ikeo Kazuho
Laboratory of DNA Data Analysis, National Institute of Genetics, Shizuoka, 411-8540, Japan.
Saito Tsuyoshi
Department of Obsterics and Gynecology, School of Medicine, Sapporo Medical University, Hokkaido, 060-0061, Japan.
Kaneko Shuich
Department of Disease Control and Homeostasis, Faculty of Medicine, Kanazawa University, Ishikawa, 920-8641, Japan.
Suzuki Yutaka
Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, 277-8561, Japan.
Hattori Masahira
Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, 277-8561, Japan. | Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 169-8555, Japan.
Matsushima Kouji
Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
Torigoe Toshihiko
CREST, Japan Science and Technology Agency, Tokyo, 102-0076, Japan. | Department of Pathology, School of Medicine, Sapporo Medical University, Hokkaido, 060-0061, Japan.
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Article Info
Journal
Scientific reports
Abbr.
Sci Rep
ISSN
2045-2322
DOI
10.1038/s41598-017-14676-3
Email
hashimoto@med.kanazawa-u.ac.jp
Published
2017-00-27
Epub
2017-00-27
Pages
14225
Language
English
Region
England
NLM ID
101563288
PMCID
PMC5660171
Subset
IM
External Links
PubMed source DOI: 10.1038/s41598-017-14676-3 PMC Full Text View journal details
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