Journal
NATURE CELL BIOLOGY
Volume 21, Issue 9, Pages 1164-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41556-019-0383-5
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Funding
- National Basic Research Program of China [2017YFA0103402]
- National Natural Science Foundation of China [31571487, 31771607]
- Peking-Tsinghua Center for Life Sciences
- 1000 Youth Talents Program of China
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Single-cell measurement of chromatin states, including histone modifications and non-histone protein binding, remains challenging. Here, we present a low-cost, efficient, simultaneous indexing and tagmentation-based ChIP-seq (itChIP-seq) method, compatible with both low cellular input and single cells for profiling chromatin states. itChIP combines chromatin opening, simultaneous cellular indexing and chromatin tagmentation within a single tube, enabling the processing of samples from tens of single cells to, more commonly, thousands of single cells per assay. We demonstrate that single-cell itChIP-seq (sc-itChIP-seq) yields similar to 9,000 unique reads per cell. Using sc-itChIP-seq to profile H3K27ac, we sufficiently capture the earliest epigenetic priming event during the cell fate transition from naive to primed pluripotency, and reveal the basis for cell-type specific enhancer usage during the differentiation of bipotent cardiac progenitor cells into endothelial cells and cardiomyocytes. Our results demonstrate that itChIP is a widely applicable technology for single-cell chromatin profiling of epigenetically heterogeneous cell populations in many biological processes.
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