Single-cell multiomics analysis reveals regulatory programs in clear cell renal cell carcinoma.
Single-cell multiomics analysis reveals regulatory programs in clear cell renal cell carcinoma.
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单细胞多组学分析揭示透明细胞肾细胞癌的调控程序
DOI：
10.1038/s41421-022-00415-0
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发表时间：
2022-07-19
期刊：
影响因子：
33.5
通讯作者：
Wen J
中科院分区：
文献类型：
--
作者：
Long Z;Sun C;Tang M;Wang Y;Ma J;Yu J;Wei J;Ma J;Wang B;Xie Q;Wen J
The clear cell renal cell carcinoma (ccRCC) microenvironment consists of many different cell types and structural components that play critical roles in cancer progression and drug resistance, but the cellular architecture and underlying gene regulatory features of ccRCC have not been fully characterized. Here, we applied single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to generate transcriptional and epigenomic landscapes of ccRCC. We identified tumor cell-specific regulatory programs mediated by four key transcription factors (TFs) (HOXC5, VENTX, ISL1, and OTP), and these TFs have prognostic significance in The Cancer Genome Atlas (TCGA) database. Targeting these TFs via short hairpin RNAs (shRNAs) or small molecule inhibitors decreased tumor cell proliferation. We next performed an integrative analysis of chromatin accessibility and gene expression for CD8+ T cells and macrophages to reveal the different regulatory elements in their subgroups. Furthermore, we delineated the intercellular communications mediated by ligand–receptor interactions within the tumor microenvironment. Taken together, our multiomics approach further clarifies the cellular heterogeneity of ccRCC and identifies potential therapeutic targets.
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T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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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
单细胞染色质可及性识别胰岛细胞类型和特定州糖尿病风险的调节计划。
影响因子：
30.8
作者：
Chiou, Joshua;Zeng, Chun;Cheng, Zhang;Han, Jee Yun;Schlichting, Michael;Miller, Michael;Mendez, Robert;Huang, Serina;Wang, Jinzhao;Sui, Yinghui;Deogaygay, Allison;Okino, Mei-Lin;Qiu, Yunjiang;Sun, Ying;Kudtarkar, Parul;Fang, Rongxin;Preissl, Sebastian;Sander, Maike;Gorkin, David U.;Gaulton, Kyle J.
通讯作者：
Gaulton, Kyle J.
影响因子：
14.8
作者：
Efremova, Mirjana;Vento-Tormo, Miquel;Vento-Tormo, Roser
通讯作者：
Vento-Tormo, Roser
影响因子：
14.9
作者：
Haeussler M;Zweig AS;Tyner C;Speir ML;Rosenbloom KR;Raney BJ;Lee CM;Lee BT;Hinrichs AS;Gonzalez JN;Gibson D;Diekhans M;Clawson H;Casper J;Barber GP;Haussler D;Kuhn RM;Kent WJ
通讯作者：
Kent WJ