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

全面的单细胞转录组分析揭示子宫内膜样腺癌组织的异质性

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作者:Shinichi Hashimoto, Yuta Tabuchi, Hideaki Yurino, Yoshihiko Hirohashi, Shungo Deshimaru, Takuya Asano, Tasuku Mariya, Kenshiro Oshima, Yuzuru Takamura, Yoshiaki Ukita, Akio Ametani, Naoto Kondo, Norikazu Monma, Tadayuki Takeda, Sadahiko Misu, Toshitugu Okayama, Kazuho Ikeo, Tsuyoshi Saito, Shuich Ka

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.

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