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  3. 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

  • Cell Discov. 2022 Jul 19;8(1):68. doi: 10.1038/s41421-022-00415-0.
Zhilin Long 1 2 3 4,  Chengfang Sun 5,  Min Tang 6,  Yin Wang 2 3 4,  Jiayan Ma 2 3 4,  Jichuan Yu 2 3 4,  Jingchao Wei 5,  Jianzhu Ma 7,  Bohan Wang 8,  Qi Xie 9 10 11,  Jiaming Wen 12
Affiliations

Affiliations

  • 1 College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
  • 2 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
  • 3 Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
  • 4 Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.
  • 5 Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • 6 Department of NanoEngineering, University of California San Diego, La Jolla, CA, USA.
  • 7 Institute for Artificial Intelligence, Peking University, Beijing, China.
  • 8 Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. wangbohan@zju.edu.cn.
  • 9 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China. xieqi@westlake.edu.cn.
  • 10 Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China. xieqi@westlake.edu.cn.
  • 11 Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China. xieqi@westlake.edu.cn.
  • 12 Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. wenjiaming@zju.edu.cn.
PMID: 35853872 DOI: 10.1038/s41421-022-00415-0
Abstract

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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