Journal
NATURE BIOTECHNOLOGY
Volume 33, Issue 11, Pages 1165-U91Publisher
NATURE PORTFOLIO
DOI: 10.1038/nbt.3383
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Funding
- Howard Hughes Medical Institute
- National Human Genome Research Institute's Centers of Excellence in Genome Sciences [P50HG006193]
- ENCODE Project [U54HG006991]
- National Heart, Lung, and Blood Institute [U01HL100395]
- National Science Foundation [DMR-1310266]
- Harvard Materials Research Science and Engineering Center [DMR-1420570]
- Defense Advanced Research Projects Agency [HR0011-11-C-0093]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1310266] Funding Source: National Science Foundation
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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.
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