Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Institute of Bioscience, University of Sao Paulo, Sao Paulo, Brazil.
Nat Genet. 2020 Nov;52(11):1208-1218. doi: 10.1038/s41588-020-00726-6. Epub 2020 Oct 30.
Cultured cell lines are the workhorse of cancer research, but the extent to which they recapitulate the heterogeneity observed among malignant cells in tumors is unclear. Here we used multiplexed single-cell RNA-seq to profile 198 cancer cell lines from 22 cancer types. We identified 12 expression programs that are recurrently heterogeneous within multiple cancer cell lines. These programs are associated with diverse biological processes, including cell cycle, senescence, stress and interferon responses, epithelial-mesenchymal transition and protein metabolism. Most of these programs recapitulate those recently identified as heterogeneous within human tumors. We prioritized specific cell lines as models of cellular heterogeneity and used them to study subpopulations of senescence-related cells, demonstrating their dynamics, regulation and unique drug sensitivities, which were predictive of clinical response. Our work describes the landscape of heterogeneity within diverse cancer cell lines and identifies recurrent patterns of heterogeneity that are shared between tumors and specific cell lines.
细胞培养系是癌症研究的主力军，但它们在多大程度上能够重现肿瘤中恶性细胞的异质性尚不清楚。在这里，我们使用多重单细胞 RNA-seq 对来自 22 种癌症类型的 198 种癌细胞系进行了分析。我们鉴定出 12 个在多个癌细胞系中反复出现的表达程序。这些程序与多种生物学过程有关，包括细胞周期、衰老、应激和干扰素反应、上皮-间充质转化和蛋白质代谢。这些程序中的大多数都能重现最近在人类肿瘤中发现的异质性。我们将特定的细胞系确定为细胞异质性的模型，并使用它们来研究与衰老相关的细胞亚群，证明了它们的动态、调控和独特的药物敏感性，这些敏感性可以预测临床反应。我们的工作描述了不同癌细胞系中异质性的全景，并确定了肿瘤和特定细胞系之间共享的反复出现的异质性模式。
