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.

  • Research Briefing
  • Published:

Quantitative profiling of regulatory DNA activity at single-cell resolution

We developed a two-pronged strategy to functionally probe the enormous repertoire of noncoding DNA within genomes. Our approach markedly improved signal-to-noise ratio and successfully intersected single-cell genomics with reporter assays. The result delivers a multiplex and highly quantitative readout of regulatory sequences’ activity in dynamic and multicellular systems.

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

Access options

Buy this article

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

Fig. 1: scQers provide a high-sensitivity readout of CRE activity.

References

  1. The ENCODE Project Consortium. et al. Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 583, 699–710 (2020). An overview article presenting the vast catalogue of regulatory elements in mammalian genomes.

    Article  CAS  Google Scholar 

  2. Patwardhan, R. P. et al. High-resolution analysis of DNA regulatory elements by synthetic saturation mutagenesis. Nat. Biotechnol. 27, 1173–1175 (2009). This paper reports the massively parallel reporter assay strategy to profile the function of regulatory DNA at scale.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Litke, J. L. & Jaffrey, S. R. Highly efficient expression of circular RNA aptamers in cells using autocatalytic transcripts. Nat. Biotechnol. 37, 667–675 (2019). This paper introduces the Tornado system to stabilize short polymerase III-driven RNAs.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhao, S. et al. A single-cell massively parallel reporter assay detects cell-type-specific gene regulation. Nat. Genet. 55, 346–354 (2023). This paper reports an assay that combines scRNA-seq with multiplex reporters.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mangan, R. J. et al. Adaptive sequence divergence forged new neurodevelopmental enhancers in humans. Cell 185, 4587–4603.e23 (2022). This paper presents another example of an assay that combines scRNA-seq with STARR-seq.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Lalanne, J.-B. et al. Multiplex profiling of developmental cis-regulatory elements with quantitative single-cell expression reporters. Nat. Methods https://doi.org/10.1038/s41592-024-02260-3 (2024).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Quantitative profiling of regulatory DNA activity at single-cell resolution. Nat Methods 21, 936–937 (2024). https://doi.org/10.1038/s41592-024-02261-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41592-024-02261-2

Search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research