Pan-cancer single-cell RNA-seq identifies recurring programs of cellular heterogeneity.
Pan-cancer single-cell RNA-seq identifies recurring programs of cellular heterogeneity.
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DOI：
10.1038/s41588-020-00726-6
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发表时间：
2020-11
期刊：
影响因子：
30.8
通讯作者：
Tirosh I
中科院分区：
文献类型：
--
作者：
Kinker GS;Greenwald AC;Tal R;Orlova Z;Cuoco MS;McFarland JM;Warren A;Rodman C;Roth JA;Bender SA;Kumar B;Rocco JW;Fernandes PACM;Mader CC;Keren-Shaul H;Plotnikov A;Barr H;Tsherniak A;Rozenblatt-Rosen O;Krizhanovsky V;Puram SV;Regev A;Tirosh I
培养的细胞系是癌症研究的主力，但目前还不清楚它们在多大程度上重现了在肿瘤中恶性细胞中观察到的细胞异质性。为了解决这个问题，我们使用多重单细胞RNA-seq对来自22种癌症类型的约200种癌细胞系进行了分析。我们发现了12个在许多癌细胞系中反复异质的表达程序。这些程序与多种生物学过程相关，包括细胞周期、衰老、应激和干扰素反应、上皮-间充质转化以及蛋白质成熟和降解。值得注意的是，大多数这些经常性的异质性程序概括了最近在人类肿瘤中观察到的那些。与肿瘤的相似性使我们能够优先考虑特定的细胞系作为细胞异质性的模型系统。我们使用两个这样的模型来证明在细胞系和肿瘤内的细胞亚群中观察到的上皮衰老相关程序的调节和动力学。我们进一步证明了这些亚群独特的药物反应，突出了其潜在的临床意义。我们的工作描述了不同癌细胞系内细胞异质性的景观，并确定了肿瘤和特定细胞系之间共享的异质性的复发模式。
Cultured cell lines are the workhorse of cancer research, but it is unclear to what extent they recapitulate the cellular heterogeneity observed among malignant cells in tumors. To address this, we used multiplexed single cell RNA-seq to profile ~200 cancer cell lines from 22 cancer types. We uncovered 12 expression programs that are recurrently heterogeneous within many cancer cell lines. These programs are associated with diverse biological processes including cell cycle, senescence, stress and interferon responses, epithelial-mesenchymal transition, and protein maturation and degradation. Notably, most of these recurrent programs of heterogeneity recapitulate those recently observed within human tumors. The similarity to tumors allowed us to prioritize specific cell lines as model systems of cellular heterogeneity. We used two such models to demonstrate the regulation and dynamics of an epithelial senescence-related program that is observed in subpopulations of cells within cell lines and tumors. We further demonstrate unique drug responses of these subpopulations, highlighting their potential clinical significance. Our work describes the landscape of cellular heterogeneity within diverse cancer cell lines, and identifies recurrent patterns of heterogeneity that are shared between tumors and specific cell lines.
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DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.1111/j.1600-0749.2006.00322.x
发表时间：
2006-08-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Hoek, Keith S.;Schlegel, Natalie C.;Dummer, Reinhard
通讯作者：
Dummer, Reinhard
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
50.3
作者：
Elkabets M;Pazarentzos E;Juric D;Sheng Q;Pelossof RA;Brook S;Benzaken AO;Rodon J;Morse N;Yan JJ;Liu M;Das R;Chen Y;Tam A;Wang H;Liang J;Gurski JM;Kerr DA;Rosell R;Teixidó C;Huang A;Ghossein RA;Rosen N;Bivona TG;Scaltriti M;Baselga J
通讯作者：
Baselga J
复制性衰老与特定转录因子结合位点处的核重组和DNA甲基化有关。
影响因子：
5.7
作者：
Hänzelmann S;Beier F;Gusmao EG;Koch CM;Hummel S;Charapitsa I;Joussen S;Benes V;Brümmendorf TH;Reid G;Costa IG;Wagner W
通讯作者：
Wagner W