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Nat Biotechnol DOI:10.1038/nbt.3383

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

Publication TypeJournal Article
Year of Publication2015
AuthorsRotem, A, Ram, O, Shoresh, N, Sperling, RA, Goren, A, Weitz, DA, Bernstein, BE
JournalNat Biotechnol
Date Published2015 Nov
KeywordsAnimals, Chromatin, Chromatin Immunoprecipitation, Computational Biology, DNA Barcoding, Taxonomic, Embryonic Stem Cells, Humans, Mice, Microfluidic Analytical Techniques, Sequence Analysis, DNA, Single-Cell Analysis

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.


Alternate JournalNat. Biotechnol.
PubMed ID26458175
PubMed Central IDPMC4636926
Grant ListP50HG006193 / HG / NHGRI NIH HHS / United States
U01HL100395 / HL / NHLBI NIH HHS / United States
U54 HG006991 / HG / NHGRI NIH HHS / United States
U54HG006991 / HG / NHGRI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States