Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells.
Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells.
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DOI：
10.1038/s41588-023-01386-y
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发表时间：
2023-05
期刊：
影响因子：
30.8
通讯作者：
Henssen, Anton G.
中科院分区：
文献类型：
--
作者：
Gonzalez, Rocio Chamorro;Conrad, Thomas;Stoeber, Maja C.;Xu, Robin;Giurgiu, Madalina;Rodriguez-Fos, Elias;Kasack, Katharina;Brueckner, Lotte;van Leen, Eric;Helmsauer, Konstantin;Garcia, Heathcliff Dorado;Stefanova, Maria E.;Hung, King L.;Bei, Yi;Schmelz, Karin;Lodrini, Marco;Mundlos, Stefan;Chang, Howard Y.;Deubzer, Hedwig E.;Sauer, Sascha;Eggert, Angelika;Schulte, Johannes H.;Schwarz, Roland F.;Haase, Kerstin;Koche, Richard P.;Henssen, Anton G.
染色体外dna （ecDNAs）在癌症中很常见，但关于其起源、结构动力学和对肿瘤内异质性的影响等许多问题仍未解决。在这里，我们描述了单细胞染色体外环状DNA和转录组测序（scEC&T-seq），这是一种对单细胞环状DNA和全长mRNA进行平行测序的方法。通过将scEC&T-seq应用于癌细胞，我们描述了细胞间ecDNA含量的差异，同时研究了它们的结构异质性和转录影响。含癌基因的ecdna克隆存在于癌细胞中，驱动细胞间癌基因表达差异。相比之下，其他小的环状dna只存在于单个细胞中，这表明它们在选择和繁殖方面存在差异。细胞间ecDNA结构的差异表明环状重组是ecDNA进化的一种机制。这些结果表明，scEC&T-seq是一种系统地表征癌细胞中小环状和大环状DNA的方法，这将有助于分析癌症和其他癌症中的这些DNA元素。scEC&T-seq分析单个人类癌细胞的染色体外环状DNA和全长mRNA，可用于询问细胞系和原发肿瘤样本的异质性。
Extrachromosomal DNAs (ecDNAs) are common in cancer, but many questions about their origin, structural dynamics and impact on intratumor heterogeneity are still unresolved. Here we describe single-cell extrachromosomal circular DNA and transcriptome sequencing (scEC&T-seq), a method for parallel sequencing of circular DNAs and full-length mRNA from single cells. By applying scEC&T-seq to cancer cells, we describe intercellular differences in ecDNA content while investigating their structural heterogeneity and transcriptional impact. Oncogene-containing ecDNAs were clonally present in cancer cells and drove intercellular oncogene expression differences. In contrast, other small circular DNAs were exclusive to individual cells, indicating differences in their selection and propagation. Intercellular differences in ecDNA structure pointed to circular recombination as a mechanism of ecDNA evolution. These results demonstrate scEC&T-seq as an approach to systematically characterize both small and large circular DNA in cancer cells, which will facilitate the analysis of these DNA elements in cancer and beyond. scEC&T-seq profiles extrachromosomal circular DNA and full-length mRNA from single human cancer cells, and may be used to interrogate heterogeneity in both cell lines and primary tumor samples.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1093/bioinformatics/btv562
发表时间：
2016-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Gel B;Díez-Villanueva A;Serra E;Buschbeck M;Peinado MA;Malinverni R
通讯作者：
Malinverni R
影响因子：
8
作者：
Cohen, S;Regev, A;Lavi, S
通讯作者：
Lavi, S
影响因子：
30.8
作者：
Koche, Richard P.;Rodriguez-Fos, Elias;Henssen, Anton G.
通讯作者：
Henssen, Anton G.
影响因子：
64.5
作者：
Hadi K;Yao X;Behr JM;Deshpande A;Xanthopoulakis C;Tian H;Kudman S;Rosiene J;Darmofal M;DeRose J;Mortensen R;Adney EM;Shaiber A;Gajic Z;Sigouros M;Eng K;Wala JA;Wrzeszczyński KO;Arora K;Shah M;Emde AK;Felice V;Frank MO;Darnell RB;Ghandi M;Huang F;Dewhurst S;Maciejowski J;de Lange T;Setton J;Riaz N;Reis-Filho JS;Powell S;Knowles DA;Reznik E;Mishra B;Beroukhim R;Zody MC;Robine N;Oman KM;Sanchez CA;Kuhner MK;Smith LP;Galipeau PC;Paulson TG;Reid BJ;Li X;Wilkes D;Sboner A;Mosquera JM;Elemento O;Imielinski M
通讯作者：
Imielinski M