Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Entering the era of single-cell transcriptomics in biology and medicine

Nature Methods volume 11, pages 22–24 (2014)Cite this article

Subjects

Recent technical advances have enabled RNA sequencing (RNA-seq) in single cells. Exploratory studies have already led to insights into the dynamics of differentiation, cellular responses to stimulation and the stochastic nature of transcription. We are entering an era of single-cell transcriptomics that holds promise to substantially impact biology and medicine.

Our notion of transcriptomes has been forged mainly by population-level observations that have been the mainstream in biology over the last two decades. We are used to thinking about differences in expression in terms of graded or subtle fold changes when comparing data across entire tissues or conditions. But the actual differences between cells may be far larger. Subsets of cells may experience dramatic changes that are averaged out or diluted by the presence of a large number of nonresponsive cells. In fact, it was shown over 60 years ago that inductive cues often result in all-or-none responses in single cells but these responses are observed as a gradual increase when quantified across the population1.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Single-cell transcriptome analyses of tissues and cell types.

References

  1. Novick, A. & Weiner, M. Proc. Natl. Acad. Sci. USA 43, 553–566 (1957).

    Article  CAS  Google Scholar 

  2. Brady, G., Barbara, M. & Iscove, N.N. Methods Mol. Biol. 2, 17–25 (1990).

    CAS  Google Scholar 

  3. Eberwine, J. et al. Proc. Natl. Acad. Sci. USA 89, 3010–3014 (1992).

    Article  CAS  Google Scholar 

  4. Islam, S. et al. Nat. Protoc. 7, 813–828 (2012).

    Article  CAS  Google Scholar 

  5. Tang, F. et al. Nat. Protoc. 5, 516–535 (2010).

    Article  CAS  Google Scholar 

  6. Picelli, S. et al. Nat. Protocols, doi:10.1038/nprot.2014.006 (2 January 2014).

  7. Yan, L. et al. Nat. Struct. Mol. Biol. 20, 1131–1139 (2013).

    Article  CAS  Google Scholar 

  8. Tang, F. et al. Cell Stem Cell 6, 468–478 (2010).

    Article  CAS  Google Scholar 

  9. Ramsköld, D. et al. Nat. Biotechnol. 30, 777–782 (2012).

    Article  Google Scholar 

  10. Islam, S. et al. Genome Res. 21, 1160–1167 (2011).

    Article  CAS  Google Scholar 

  11. Picelli, S. et al. Nat. Methods 10, 1096–1098 (2013).

    Article  CAS  Google Scholar 

  12. Kivioja, T. et al. Nat. Methods 9, 72–74 (2012).

    Article  CAS  Google Scholar 

  13. Hashimshony, T., Wagner, F., Sher, N. & Yanai, I. Cell Rep 2, 666–673 (2012).

    Article  CAS  Google Scholar 

  14. Shapiro, E., Biezuner, T. & Linnarsson, S. Nat. Rev. Genet. 14, 618–630 (2013).

    Article  CAS  Google Scholar 

  15. Dominissini, D. et al. Nature 485, 201–206 (2012).

    Article  CAS  Google Scholar 

  16. Raj, A. & van Oudenaarden, A. Cell 135, 216–226 (2008).

    Article  CAS  Google Scholar 

  17. Chubb, J.R., Trcek, T., Shenoy, S.M. & Singer, R.H. Curr. Biol. 16, 1018–1025 (2006).

    Article  CAS  Google Scholar 

  18. Wills, Q.F. et al. Nat. Biotechnol. 31, 748–752 (2013).

    Article  CAS  Google Scholar 

  19. McDavid, A. et al. Bioinformatics 29, 461–467 (2013).

    Article  CAS  Google Scholar 

  20. Mercer, T.R. et al. Nat. Biotechnol. 30, 99–104 (2012).

    Article  CAS  Google Scholar 

  21. Wang, E.T. et al. Nature 456, 470–476 (2008).

    Article  CAS  Google Scholar 

  22. Shalek, A.K. et al. Nature 498, 236–240 (2013).

    Article  CAS  Google Scholar 

  23. Sandberg, R., Neilson, J.R., Sarma, A., Sharp, P.A. & Burge, C.B. Science 320, 1643–1647 (2008).

    Article  CAS  Google Scholar 

  24. Mayr, C. & Bartel, D.P. Cell 138, 673–684 (2009).

    Article  CAS  Google Scholar 

  25. Rhodes, D.R. et al. Proc. Natl. Acad. Sci. USA 101, 9309–9314 (2004).

    Article  CAS  Google Scholar 

  26. Golub, T.R. et al. Science 286, 531–537 (1999).

    Article  CAS  Google Scholar 

  27. Dalerba, P. et al. Nat. Biotechnol. 29, 1120–1127 (2011).

    Article  CAS  Google Scholar 

  28. Gerlinger, M. et al. N. Engl. J. Med. 366, 883–892 (2012).

    Article  CAS  Google Scholar 

  29. Yu, M. et al. Nature 487, 510–513 (2012).

    Article  CAS  Google Scholar 

  30. Vogelstein, B. et al. Science 339, 1546–1558 (2013).

    Article  CAS  Google Scholar 

  31. Kim, H.D., Shay, T., O'Shea, E.K. & Regev, A. Science 325, 429–432 (2009).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I am grateful to B. Reinius, J. Muhr, J. Holmberg and members of the Sandberg laboratory for comments on the manuscript. R.S. is supported by the European Research Council Starting grant 243066, the Swedish Foundation for Strategic Research FFL4 and the Swedish Research Council grant 2008-4562.

Author information

Authors and Affiliations

  1. and Department of Cell and Molecular Biology, Rickard Sandberg is at the Ludwig Institute for Cancer Research, Stockholm, Sweden, Karolinska Institutet, Stockholm, Sweden.,

    Rickard Sandberg

Authors
  1. Rickard Sandberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rickard Sandberg.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sandberg, R. Entering the era of single-cell transcriptomics in biology and medicine. Nat Methods 11, 22–24 (2014). https://doi.org/10.1038/nmeth.2764

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth.2764

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing