Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin

Sai Ma, Bing Zhang, Lindsay M. LaFave, Andrew S. Earl, Zachary Chiang, Yan Hu, Jiarui Ding, Alison Brack, Vinay K. Kartha, Tristan Tay, Travis Law, Caleb Lareau, Ya Chieh Hsu, Aviv Regev, Jason D. Buenrostro

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Cell differentiation and function are regulated across multiple layers of gene regulation, including modulation of gene expression by changes in chromatin accessibility. However, differentiation is an asynchronous process precluding a temporal understanding of regulatory events leading to cell fate commitment. Here we developed simultaneous high-throughput ATAC and RNA expression with sequencing (SHARE-seq), a highly scalable approach for measurement of chromatin accessibility and gene expression in the same single cell, applicable to different tissues. Using 34,774 joint profiles from mouse skin, we develop a computational strategy to identify cis-regulatory interactions and define domains of regulatory chromatin (DORCs) that significantly overlap with super-enhancers. During lineage commitment, chromatin accessibility at DORCs precedes gene expression, suggesting that changes in chromatin accessibility may prime cells for lineage commitment. We computationally infer chromatin potential as a quantitative measure of chromatin lineage-priming and use it to predict cell fate outcomes. SHARE-seq is an extensible platform to study regulatory circuitry across diverse cells in tissues.

Original languageEnglish (US)
Pages (from-to)1103-1116.e20
JournalCell
Volume183
Issue number4
DOIs
StatePublished - Nov 12 2020
Externally publishedYes

Keywords

  • epigenomics
  • gene regulation
  • single cell
  • skin
  • stem cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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