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Applications of single-cell sequencing in cancer research: progress and perspectives.

文献信息

DOI10.1186/s13045-021-01105-2
PMID34108022
期刊Journal of hematology & oncology
影响因子40.4
JCR 分区Q1
发表年份2021
被引次数303
关键词循环肿瘤细胞, 异质性, 微环境, 单细胞测序
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN1756-8722
页码91
期号14(1)
作者Yalan Lei, Rong Tang, Jin Xu, Wei Wang, Bo Zhang, Jiang Liu, Xianjun Yu, Si Shi

一句话小结

单细胞测序技术在癌症研究中提供了以单细胞分辨率解读肿瘤异质性和免疫细胞特性的能力,显著改善了对癌症生物特性和动态变化的理解。该技术的进步有助于提升癌症的诊断、靶向治疗和预后预测,为患者提供更精准的治疗靶点。

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循环肿瘤细胞 · 异质性 · 微环境 · 单细胞测序

摘要

单细胞测序,包括基因组学、转录组学、表观基因组学、蛋白质组学和代谢组学测序,是一种强大的工具,能够以单细胞分辨率解读细胞和分子景观,这与提供平均数据的总体测序不同。单细胞测序在癌症研究中的应用彻底改变了我们对癌症病灶内生物特性和动态的理解。在本综述中,我们总结了新兴的单细胞测序技术及通过单细胞测序获得的最新癌症研究进展,包括与恶性细胞和免疫细胞的景观、肿瘤异质性、循环肿瘤细胞及肿瘤生物行为潜在机制相关的信息。总体而言,单细胞测序在促进各种肿瘤的诊断、靶向治疗和预后预测方面的前景非常光明。展望未来,单细胞测序的进展无疑将改善我们对肿瘤生物特性的理解,并为患者突出潜在的精准治疗靶点。

英文摘要

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics sequencing, is a powerful tool to decipher the cellular and molecular landscape at a single-cell resolution, unlike bulk sequencing, which provides averaged data. The use of single-cell sequencing in cancer research has revolutionized our understanding of the biological characteristics and dynamics within cancer lesions. In this review, we summarize emerging single-cell sequencing technologies and recent cancer research progress obtained by single-cell sequencing, including information related to the landscapes of malignant cells and immune cells, tumor heterogeneity, circulating tumor cells and the underlying mechanisms of tumor biological behaviors. Overall, the prospects of single-cell sequencing in facilitating diagnosis, targeted therapy and prognostic prediction among a spectrum of tumors are bright. In the near future, advances in single-cell sequencing will undoubtedly improve our understanding of the biological characteristics of tumors and highlight potential precise therapeutic targets for patients.

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主要研究问题

  1. 单细胞测序在癌症研究中的具体应用有哪些,如何改变了我们对肿瘤生物学的理解?
  2. 单细胞测序技术的最新进展如何影响肿瘤异质性的研究?
  3. 在单细胞测序中,如何识别和分析循环肿瘤细胞对癌症诊断的意义?
  4. 单细胞测序在靶向治疗和预后预测中的潜在应用有哪些?
  5. 有哪些挑战和局限性需要克服,以进一步推动单细胞测序在癌症研究中的应用?

核心洞察

研究背景和目的

单细胞测序技术(Single-cell sequencing, SCS)是近年来生物医学领域的重要进展,能够以单细胞分辨率解读细胞和分子景观,极大地推动了癌症研究的进展。本综述旨在总结单细胞测序技术的最新发展及其在癌症研究中的应用,探讨肿瘤异质性、肿瘤微环境及循环肿瘤细胞的动态变化。

主要方法/材料/实验设计

单细胞测序技术包括多种平台和方法,主要分为以下几类:

  1. 单细胞转录组测序(scRNA-seq):用于分析单个细胞的基因表达。
  2. 单细胞基因组测序:识别单个细胞的遗传变异。
  3. 单细胞表观基因组测序:研究细胞的表观遗传特征。
  4. 单细胞蛋白质组学:分析单细胞内的蛋白质表达。

技术流程图

Mermaid diagram

关键结果和发现

  1. 肿瘤异质性:单细胞测序揭示了肿瘤细胞内的显著异质性,识别出多种肿瘤亚群及其特征,影响治疗反应和预后。
  2. 肿瘤微环境:研究表明肿瘤微环境中的免疫细胞和基质细胞在肿瘤进展和耐药性中发挥重要作用。
  3. 循环肿瘤细胞(CTCs):单细胞分析提供了对CTCs的深刻见解,揭示了其在转移过程中的角色及潜在的生物标志物。

主要结论/意义/创新性

单细胞测序技术的应用使我们能够深入理解肿瘤的生物学特性和动态变化,促进了精准医学的发展。该技术不仅有助于识别新的治疗靶点,还为癌症的早期诊断和预后评估提供了新思路。

研究局限性和未来方向

尽管单细胞测序技术在癌症研究中展现出巨大的潜力,但仍存在一些局限性,如测序的灵敏度和准确性问题、样本处理的复杂性及批次效应等。未来的研究应集中于:

  • 提高单细胞测序的准确性和通量。
  • 开发集成多组学的方法,以更全面地描绘肿瘤的生物特征。
  • 在临床试验中验证这些技术的有效性,以推动其在临床应用中的普及。

通过克服这些挑战,单细胞测序有望为癌症研究和治疗提供更强大的工具和方法。

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  1. Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing - Review. - Gabriel Dorado;Sergio Gálvez;Teresa E Rosales;Víctor F Vásquez;Pilar Hernández - Biomolecules (2021)
  2. Trends in the Research Into Immune Checkpoint Blockade by Anti-PD1/PDL1 Antibodies in Cancer Immunotherapy: A Bibliometric Study. - Yiting Sun;Liqing Jiang;Ti Wen;Xiaoyu Guo;Xinye Shao;Hui Qu;Xi Chen;Yujia Song;Fang Wang;Xiujuan Qu;Zhi Li - Frontiers in pharmacology (2021)
  3. High-Throughput Strategies for the Discovery of Anticancer Drugs by Targeting Transcriptional Reprogramming. - Lijun Huang;Xiaohong Yi;Xiankuo Yu;Yumei Wang;Chen Zhang;Lixia Qin;Dale Guo;Shiyi Zhou;Guanbin Zhang;Yun Deng;Xilinqiqige Bao;Dong Wang - Frontiers in oncology (2021)
  4. Application of Single-Cell Multi-Omics in Dissecting Cancer Cell Plasticity and Tumor Heterogeneity. - Deshen Pan;Deshui Jia - Frontiers in molecular biosciences (2021)
  5. Tumor Heterogeneity and Consequences for Bladder Cancer Treatment. - Etienne Lavallee;John P Sfakianos;David J Mulholland - Cancers (2021)
  6. Single-Cell Sequencing: Biological Insight and Potential Clinical Implications in Pediatric Leukemia. - Donát Alpár;Bálint Egyed;Csaba Bödör;Gábor T Kovács - Cancers (2021)
  7. Evolution and Targeting of Myeloid Suppressor Cells in Cancer: A Translational Perspective. - Augusto Bleve;Francesca Maria Consonni;Chiara Porta;Valentina Garlatti;Antonio Sica - Cancers (2022)
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