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Series GSE96688 Query DataSets for GSE96688
Status Public on Jul 23, 2018
Title scMNase-seq measures chromatin accessibility and nucleosome positioning in single cells
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Nucleosome positioning is critical to chromatin accessibility, and is associated with gene expression programs in cells. Previous nucleosome mapping methods assemble profiles from cell populations and reveal a cell-averaged pattern: nucleosomes are positioned and form a phased array surrounding the transcription start sites (TSSs ) of active genes and DNase I hypersensitive sites (DHSs). However, cells exhibit remarkable expression heterogeneity in response to active signaling even in a homogenous population of cells, which may be related to the heterogeneity in chromatin accessibility. Here, we report a technique, termed single-cell MNase-seq (scMNase-seq), to measure genome-wide nucleosome positioning and chromatin accessibility simultaneously in single cells. Application of scMNase-seq to NIH3T3, mouse primary naïve CD4 T and embryonic stem cells (mESC) reveals two novel principles of nucleosome organization: (1) nucleosomes surrounding TSSs of silent genes or in heterochromatin regions show large positioning variation across different cells but are highly uniformly spaced along the nucleosome array and, (2) In contrast, nucleosomes surrounding TSSs of active genes and DHSs show small positioning variation across different cells but show relatively low spacing uniformness along the nucleosome array. We found a bimodal distribution of nucleosome spacing at DHSs, which corresponds to inaccessible and accessible states and is associated with nucleosome variation and accessibility variation across cells. Nucleosome variation within single cells is smaller than that across cells and variation within the same cell type is smaller than that across cell types. A large fraction of naïve CD4 T cells and mESCs show depleted nucleosome occupancy at the de novo enhancers detected in their respectively differentiated lineages, revealing the existence of cells primed for differentiation to specific lineages in undifferentiated cell populations.
Overall design Measuring chromatin accessibility and nucleosome positioning in single-cells by applying single-cell MNase-seq to 48 NIH3T3 cells, 198 mouse embryonic stem cells (mESCs), and 278 mouse naïve CD4 T cells.
Contributor(s) Lai B, Gao W, Cui K, Xie W, Tang Q, Jin W, Hu G, Ni B, Zhao K
Citation(s) 30258225, 31836865
Submission date Mar 16, 2017
Last update date Mar 07, 2024
Contact name Keji Zhao
Organization name NHLBI,NIH
Department Systems Biology Center
Lab Laboratory of Epigenome Biology
Street address 9000 Rockville Pike
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (586)
GSM2538320 scMNase-seq_NIH3T3_GA5875
GSM2538321 scMNase-seq_NIH3T3_GA5877
GSM2538322 scMNase-seq_NIH3T3_GA5878
BioProject PRJNA379378
SRA SRP101997

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Supplementary file Size Download File type/resource
GSE96688_RAW.tar 7.3 Gb (http)(custom) TAR (of BED)
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Raw data are available in SRA
Processed data provided as supplementary file

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