Single-cell Sequencing-based Technologies Will Revolutionize Whole-organism Science

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2013 Jul 31

PMID 23897237

Citations 536

Authors

Ehud Shapiro

Tamir Biezuner

Sten Linnarsson

Affiliations

Soon will be listed here.

Abstract

The unabated progress in next-generation sequencing technologies is fostering a wave of new genomics, epigenomics, transcriptomics and proteomics technologies. These sequencing-based technologies are increasingly being targeted to individual cells, which will allow many new and longstanding questions to be addressed. For example, single-cell genomics will help to uncover cell lineage relationships; single-cell transcriptomics will supplant the coarse notion of marker-based cell types; and single-cell epigenomics and proteomics will allow the functional states of individual cells to be analysed. These technologies will become integrated within a decade or so, enabling high-throughput, multi-dimensional analyses of individual cells that will produce detailed knowledge of the cell lineage trees of higher organisms, including humans. Such studies will have important implications for both basic biological research and medicine.

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References

Kim M, Oskarsson T, Acharyya S, Nguyen D, Zhang X, Norton L . Tumor self-seeding by circulating cancer cells. Cell. 2010; 139(7):1315-26. PMC: 2810531. DOI: 10.1016/j.cell.2009.11.025. View

Fidler I . Critical determinants of metastasis. Semin Cancer Biol. 2002; 12(2):89-96. DOI: 10.1006/scbi.2001.0416. View

Kurimoto K, Yabuta Y, Ohinata Y, Ono Y, Uno K, Yamada R . An improved single-cell cDNA amplification method for efficient high-density oligonucleotide microarray analysis. Nucleic Acids Res. 2006; 34(5):e42. PMC: 1409679. DOI: 10.1093/nar/gkl050. View

Nik-Zainal S, Van Loo P, Wedge D, Alexandrov L, Greenman C, Lau K . The life history of 21 breast cancers. Cell. 2012; 149(5):994-1007. PMC: 3428864. DOI: 10.1016/j.cell.2012.04.023. View

Hayashi-Takanaka Y, Yamagata K, Wakayama T, Stasevich T, Kainuma T, Tsurimoto T . Tracking epigenetic histone modifications in single cells using Fab-based live endogenous modification labeling. Nucleic Acids Res. 2011; 39(15):6475-88. PMC: 3159477. DOI: 10.1093/nar/gkr343. View

Sulston J, Horvitz H . Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol. 1977; 56(1):110-56. DOI: 10.1016/0012-1606(77)90158-0. View

Vilkki S, Tsao J, Loukola A, Poyhonen M, Vierimaa O, Herva R . Extensive somatic microsatellite mutations in normal human tissue. Cancer Res. 2001; 61(11):4541-4. View

Kim K, Shibata D . Methylation reveals a niche: stem cell succession in human colon crypts. Oncogene. 2002; 21(35):5441-9. DOI: 10.1038/sj.onc.1205604. View

van de Werken H, Landan G, Holwerda S, Hoichman M, Klous P, Chachik R . Robust 4C-seq data analysis to screen for regulatory DNA interactions. Nat Methods. 2012; 9(10):969-72. DOI: 10.1038/nmeth.2173. View

10.

Dalerba P, Kalisky T, Sahoo D, Rajendran P, Rothenberg M, Leyrat A . Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat Biotechnol. 2011; 29(12):1120-7. PMC: 3237928. DOI: 10.1038/nbt.2038. View

11.

Kivioja T, Vaharautio A, Karlsson K, Bonke M, Enge M, Linnarsson S . Counting absolute numbers of molecules using unique molecular identifiers. Nat Methods. 2011; 9(1):72-4. DOI: 10.1038/nmeth.1778. View

12.

Shiroguchi K, Jia T, Sims P, Xie X . Digital RNA sequencing minimizes sequence-dependent bias and amplification noise with optimized single-molecule barcodes. Proc Natl Acad Sci U S A. 2012; 109(4):1347-52. PMC: 3268301. DOI: 10.1073/pnas.1118018109. View

13.

Frumkin D, Wasserstrom A, Itzkovitz S, Harmelin A, Rechavi G, Shapiro E . Amplification of multiple genomic loci from single cells isolated by laser micro-dissection of tissues. BMC Biotechnol. 2008; 8:17. PMC: 2266725. DOI: 10.1186/1472-6750-8-17. View

14.

Shi Q, Qin L, Wei W, Geng F, Fan R, Shin Y . Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells. Proc Natl Acad Sci U S A. 2011; 109(2):419-24. PMC: 3258586. DOI: 10.1073/pnas.1110865109. View

15.

Fredriksson S, Dixon W, Ji H, Koong A, Mindrinos M, Davis R . Multiplexed protein detection by proximity ligation for cancer biomarker validation. Nat Methods. 2007; 4(4):327-9. DOI: 10.1038/nmeth1020. View

16.

Lieberman-Aiden E, van Berkum N, Williams L, Imakaev M, Ragoczy T, Telling A . Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009; 326(5950):289-93. PMC: 2858594. DOI: 10.1126/science.1181369. View

17.

Guo M, Rotem A, Heyman J, Weitz D . Droplet microfluidics for high-throughput biological assays. Lab Chip. 2012; 12(12):2146-55. DOI: 10.1039/c2lc21147e. View

18.

Xu M, Fujita D, Hanagata N . Perspectives and challenges of emerging single-molecule DNA sequencing technologies. Small. 2009; 5(23):2638-49. DOI: 10.1002/smll.200900976. View

19.

Zong C, Lu S, Chapman A, Xie X . Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science. 2012; 338(6114):1622-6. PMC: 3600412. DOI: 10.1126/science.1229164. View

20.

Gundry M, Li W, Maqbool S, Vijg J . Direct, genome-wide assessment of DNA mutations in single cells. Nucleic Acids Res. 2011; 40(5):2032-40. PMC: 3300019. DOI: 10.1093/nar/gkr949. View