Single-cell ChIP-seq reveals cell subpopulations defined by chromatin state

Assaf Rotem, Oren Ram, Noam Shoresh, Ralph A. Sperling, Alon Goren, David A. Weitz, Bradley E. Bernstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

627 Scopus citations

Abstract

Chromatin profiling provides a versatile means to investigate functional genomic elements and their regulation. However, current methods yield ensemble profiles that are insensitive to cell-to-cell variation. Here we combine microfluidics, DNA barcoding and sequencing to collect chromatin data at single-cell resolution. We demonstrate the utility of the technology by assaying thousands of individual cells and using the data to deconvolute a mixture of ES cells, fibroblasts and hematopoietic progenitors into high-quality chromatin state maps for each cell type. The data from each single cell are sparse, comprising on the order of 1,000 unique reads. However, by assaying thousands of ES cells, we identify a spectrum of subpopulations defined by differences in chromatin signatures of pluripotency and differentiation priming. We corroborate these findings by comparison to orthogonal single-cell gene expression data. Our method for single-cell analysis reveals aspects of epigenetic heterogeneity not captured by transcriptional analysis alone.

Original languageAmerican English
Pages (from-to)1165-1172
Number of pages8
JournalNature Biotechnology
Volume33
Issue number11
DOIs
StatePublished - 1 Nov 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.

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