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SINGLE-CELL TECHNOLOGY

Expanding the single-cell genomics toolkit

Nature Genetics volume 51, pages 931–932 (2019)Cite this article

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Epigenetic heterogeneity underlies the diversity of cell states found in health and disease. A new study presents a method for profiling of histone modifications in single cells and applies it to identify rare chromatin states, possibly predisposed to drug resistance, within patient-derived tumor xenografts.

Epigenetic heterogeneity plays a central role in enabling genetically identical cells to take on remarkably heterogeneous states and fates, not only in development but also in disease processes such as cancer. Epigenetically permissive states have been proposed to potentially predispose rare subpopulations of cancer cells to drug resistance upon treatment1,2. How can such rare subpopulations be sensitively identified and characterized at a genome-wide scale? In the past few years, a plethora of methods have been developed for quantifying molecular heterogeneity in single cells. For example, single-cell RNA-seq measures transcriptional heterogeneity3, and single-cell ATAC–seq measures relative chromatin accessibility4,5,6. However, it has been particularly challenging to develop methods that directly interrogate histone modifications and interactions between transcription factors and DNA in single cells.

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Fig. 1: scChIP–seq for single-cell histone-modification profiling.

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Authors and Affiliations

  1. Department of Genome Sciences, University of Washington, Seattle, WA, USA

    Anna Minkina & Jay Shendure

  2. Brotman Baty Institute for Precision Medicine, Seattle, WA, USA

    Jay Shendure

  3. Allen Discovery Center for Cell Lineage Tracing, Seattle, WA, USA

    Jay Shendure

  4. Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA

    Jay Shendure

Authors
  1. Anna Minkina
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  2. Jay Shendure
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Correspondence to Jay Shendure.

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The authors declare no competing interests.

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Minkina, A., Shendure, J. Expanding the single-cell genomics toolkit. Nat Genet 51, 931–932 (2019). https://doi.org/10.1038/s41588-019-0429-4

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  • DOI: https://doi.org/10.1038/s41588-019-0429-4

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