Mass cytometric and transcriptomic profiling of epithelial-mesenchymal transitions in human mammary cell lines

人类乳腺细胞系上皮-间质转化的质谱流式细胞术和转录组学分析

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作者:Johanna Wagner, Markus Masek, Andrea Jacobs, Charlotte Soneson, Sujana Sivapatham, Nicolas Damond, Natalie de Souza, Mark D Robinson, Bernd Bodenmiller

Abstract

Epithelial-mesenchymal transition (EMT) equips breast cancer cells for metastasis and treatment resistance. However, detection, inhibition, and elimination of EMT-undergoing cells is challenging due to the intrinsic heterogeneity of cancer cells and the phenotypic diversity of EMT programs. We comprehensively profiled EMT transition phenotypes in four non-cancerous human mammary epithelial cell lines using a flow cytometry surface marker screen, RNA sequencing, and mass cytometry. EMT was induced in the HMLE and MCF10A cell lines and in the HMLE-Twist-ER and HMLE-Snail-ER cell lines by prolonged exposure to TGFβ1 or 4-hydroxytamoxifen, respectively. Each cell line exhibited a spectrum of EMT transition phenotypes, which we compared to the steady-state phenotypes of fifteen luminal, HER2-positive, and basal breast cancer cell lines. Our data provide multiparametric insights at single-cell level into the phenotypic diversity of EMT at different time points and in four human cellular models. These insights are valuable to better understand the complexity of EMT, to compare EMT transitions between the cellular models used here, and for the design of EMT time course experiments.

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