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 language | English (US) |
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Pages (from-to) | 1103-1116.e20 |
Journal | Cell |
Volume | 183 |
Issue number | 4 |
DOIs | |
State | Published - Nov 12 2020 |
Externally published | Yes |
Keywords
- epigenomics
- gene regulation
- single cell
- skin
- stem cell
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology