A multi-omic single-cell landscape of human gynecologic malignancies.
A multi-omic single-cell landscape of human gynecologic malignancies.
复制标题
人类妇科恶性肿瘤的多摩尼克单细胞景观。
DOI：
10.1016/j.molcel.2021.10.013
复制
发表时间：
2021-12-02
期刊：
影响因子：
16
通讯作者：
Franco HL
中科院分区：
文献类型：
--
作者：
Regner MJ;Wisniewska K;Garcia-Recio S;Thennavan A;Mendez-Giraldez R;Malladi VS;Hawkins G;Parker JS;Perou CM;Bae-Jump VL;Franco HL
推动癌细胞转录程序的调控机制的去卷积是理解肿瘤生物学的关键。在这里，我们提出了单细胞分辨率的匹配转录组(scRNA-seq)和染色质可及性谱(scATAC-seq)，来自手术切除后立即处理的人卵巢和子宫内膜肿瘤。这个数据集揭示了这些肿瘤复杂的细胞异质性，并使我们能够定量地将染色质可及性的变化与基因表达联系起来。我们表明，恶性细胞获得以前未被注释的调控元件来驱动标志性的癌症途径。此外，来自同一患者体内的恶性细胞在与转录输出相关的染色质可及性方面显示出很大的差异，突显了肿瘤内异质性的重要性。最后，我们推断了转录因子的恶性细胞类型特异性活性。通过定义癌细胞的调控逻辑，这项工作揭示了对致癌调控元件的重要依赖，并强调了匹配的scRNAseq/scATACseq揭示妇科癌症发生的临床相关机制的能力。Regner&Wisniewska等人。提出对单细胞转录和染色质可及性数据的综合分析，以确定人类妇科癌症中恶性细胞状态的调节逻辑。他们确定了数千个显著的癌症特异性末端调节元件，并发现了驱动肿瘤内异质性的差异转录因子活性。
Deconvolution of regulatory mechanisms that drive transcriptional programs in cancer cells is key to understanding tumor biology. Herein, we present matched transcriptome (scRNA-seq) and chromatin accessibility profiles (scATAC-seq) at single-cell resolution from human ovarian and endometrial tumors processed immediately following surgical resection. This dataset reveals the complex cellular heterogeneity of these tumors and enabled us to quantitatively link variation in chromatin accessibility to gene expression. We show that malignant cells acquire previously unannotated regulatory elements to drive hallmark cancer pathways. Moreover, malignant cells from within the same patients show substantial variation in chromatin accessibility linked to transcriptional output, highlighting the importance of intratumoral heterogeneity. Finally, we infer the malignant cell type-specific activity of transcription factors. By defining the regulatory logic of cancer cells, this work reveals an important reliance on oncogenic regulatory elements and highlights the ability of matched scRNAseq/scATACseq to uncover clinically relevant mechanisms of tumorigenesis in gynecologic cancers. Regner & Wisniewska et al. present an integrated analysis of single-cell transcriptomics and chromatin accessibility data to define the regulatory logic of malignant cell states in human gynecologic cancers. They identify thousands of salient cancer-specific distal regulatory elements and uncover differential transcription factor activity that drives intratumor heterogeneity.
登录
查看更多内容
影响因子：
50.3
作者：
Berger AC;Korkut A;Kanchi RS;Hegde AM;Lenoir W;Liu W;Liu Y;Fan H;Shen H;Ravikumar V;Rao A;Schultz A;Li X;Sumazin P;Williams C;Mestdagh P;Gunaratne PH;Yau C;Bowlby R;Robertson AG;Tiezzi DG;Wang C;Cherniack AD;Godwin AK;Kuderer NM;Rader JS;Zuna RE;Sood AK;Lazar AJ;Ojesina AI;Adebamowo C;Adebamowo SN;Baggerly KA;Chen TW;Chiu HS;Lefever S;Liu L;MacKenzie K;Orsulic S;Roszik J;Shelley CS;Song Q;Vellano CP;Wentzensen N;Cancer Genome Atlas Research Network;Weinstein JN;Mills GB;Levine DA;Akbani R
通讯作者：
Akbani R
DOI：
10.1126/science.aau0730
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cao J;Cusanovich DA;Ramani V;Aghamirzaie D;Pliner HA;Hill AJ;Daza RM;McFaline-Figueroa JL;Packer JS;Christiansen L;Steemers FJ;Adey AC;Trapnell C;Shendure J
通讯作者：
Shendure J
影响因子：
14.9
作者：
Bailey TL;Johnson J;Grant CE;Noble WS
通讯作者：
Noble WS
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
单细胞染色质可及性揭示了调节变化的原理。
影响因子：
64.8
作者：
Buenrostro JD;Wu B;Litzenburger UM;Ruff D;Gonzales ML;Snyder MP;Chang HY;Greenleaf WJ
通讯作者：
Greenleaf WJ