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

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          Abstract

          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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          Most cited references232

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          PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.

          Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade.
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            Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position.

            We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. We discovered classes of DNA-binding factors that strictly avoided, could tolerate or tended to overlap with nucleosomes. Using ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.
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              Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets.

              Cells, the basic units of biological structure and function, vary broadly in type and state. Single-cell genomics can characterize cell identity and function, but limitations of ease and scale have prevented its broad application. Here we describe Drop-seq, a strategy for quickly profiling thousands of individual cells by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell's RNAs, and sequencing them all together. Drop-seq analyzes mRNA transcripts from thousands of individual cells simultaneously while remembering transcripts' cell of origin. We analyzed transcriptomes from 44,808 mouse retinal cells and identified 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes. Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution. VIDEO ABSTRACT.
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                Author and article information

                Contributors
                yuxianjun@fudanpci.org
                shisi@fudanpci.org
                Journal
                J Hematol Oncol
                J Hematol Oncol
                Journal of Hematology & Oncology
                BioMed Central (London )
                1756-8722
                9 June 2021
                9 June 2021
                2021
                : 14
                : 91
                Affiliations
                [1 ]GRID grid.452404.3, ISNI 0000 0004 1808 0942, Department of Pancreatic Surgery, , Fudan University Shanghai Cancer Center, ; No. 270 Dong’An Road, Shanghai, 200032 China
                [2 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Department of Oncology, Shanghai Medical College, , Fudan University, ; Shanghai, China
                [3 ]GRID grid.452404.3, ISNI 0000 0004 1808 0942, Shanghai Pancreatic Cancer Institute, ; No. 270 Dong’An Road, Shanghai, 200032 China
                [4 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Pancreatic Cancer Institute, , Fudan University, ; Shanghai, China
                Author information
                http://orcid.org/0000-0002-6697-7143
                Article
                1105
                10.1186/s13045-021-01105-2
                8190846
                34108022
                12e9428d-5f01-42a2-bb49-f1404e530f8b
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 17 April 2021
                : 3 June 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81802352
                Award ID: 81902428
                Award Recipient :
                Funded by: National Natural Science Foundation of China
                Award ID: 81772555
                Award Recipient :
                Funded by: National Science Foundation for Distinguished Young Scholars of China
                Award ID: 81625016
                Award Recipient :
                Funded by: Shanghai Sailing Program
                Award ID: 19YF1409400
                Award Recipient :
                Funded by: Shanghai Sailing Program
                Award ID: 20YF1409000
                Funded by: FundRef http://dx.doi.org/10.13039/501100013105, Shanghai Rising-Star Program;
                Award ID: 20QA1402100
                Award Recipient :
                Funded by: Shanghai Anticancer Association Young Eagle Program
                Award ID: SACA-CY19A06
                Award Recipient :
                Funded by: Clinical and Scientific Innovation Project of Shanghai Hospital Development Center
                Award ID: SHDC12018109
                Award ID: SHDC12019109
                Award Recipient :
                Funded by: Scientific Innovation Project of Shanghai Education Committee
                Award ID: 2019-01-07-00-07-E00057
                Award Recipient :
                Funded by: Fudan University Shanghai Medical College Qing Feng Scholar Project
                Award ID: QF2110
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                single-cell sequencing,heterogeneity,microenvironment,circulating tumor cells

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