Single-cell chromatin accessibility reveals principles of regulatory variation

In the citing paper

“Such DNA variation data can be combined with chromatin accessibility and thus form a three-dimensional informative “regulome” in the genome (312).”

In the citing paper

“These studies revealed regulatory heterogeneity within immunophenotypically sorted cellular populations that are governed by diverse regulatory programmes at individual cis-regulatory elements and by relatively simple TF motif dynamics.”

In the citing paper

“Two methods of scATAC-seq were developed in 2015, which enabled the exploration of chromatin accessibility at the single-cell level.”

In the citing paper

“To this point, new methods have recently emerged that overcome many of the key limitations of earlier technologies. These include single-cell (‘sc’) methods to identify cell-type-specific open chromatin in complex tissues82,83; higher resolution chromosome conformation capture [G] methods to more finely map enhancer–promoter contacts84; MPRAs to dissect or trap enhancer activity on a reporter”

In the citing paper

“For example, single-cell ATAC-seq has enabled the in vivo profiling of accessible chromatin at the scale of a whole organism82,83.160,161.”

In the citing paper

“Other single-cell methods have been developed to measure single-cell DNA methylation [182] and single-cell open chromatin using ATAC-seq [183, 184].”

In the citing paper

“Note that these features were originally developed for scATAC-seq data on non-perturbed cells, with goals such as the identification of cell type, discovery of cell type-specific regulatory elements, or reconstruction of cellular differentiation trajectories43,61.”

In the citing paper

“the microfluidics approach of Buenrostro et al. can use a commercially available Tn5 transposase, whereas combinatorial indexing requires a self-made Tn5 transposase tagged with different barcodes.”

In the citing paper

“There are two experimental methods to perform scATAC-seq, either based on a microfluidic platform (Fluidigm C1) for physical isolation of single cells [58] or on combinatorial cellular indexing of sorted nuclei (sciATAC-seq) [59].”

In the citing paper

“Interestingly, scATAC-seq was able to capture the distinct regulatory states and trajectories, leading to the finding of a continuous regulatory landscape that underlies human haematopoiesis [58].”

In the citing paper

“Buenrostro et al. [58] showed that chromatin accessibility variance in K562 myeloid leukaemia cells was associated with specific TF-binding sites (including GATA1/2, JUN and STAT2).”

In the citing paper

“To overcome this intrinsic sparseness, several studies26,28 have reasoned that functionally related genomic elements, such as all the sites bound by the same transcription factor, would co-vary within the same cell (analogous to the observation above on transcript co-regulation to infer circuits), providing a higher-order aggregate signal that allows one to group cells by their shared inferred”

In the citing paper

“Similarly, simultaneous analysis of protein and RNA or of epigenomic profiles and RNA can provide mechanistic explanations that relate variations in the state of regulator proteins3 or cis-regulatory loci27,28 to variation in target transcripts.”

In the citing paper

“single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) measures genome-wide chromatin accessibility in individual cells133,134”

In the citing paper

“However, these current methods for single-cell ATAC-seq (scATAC-seq)18,19 either remain relatively low throughput (hundreds to thousands of cells per experiment) or provide low-complexity data (thousands of fragments per cell).”

In the citing paper

“Notably, dscATAC-seq recapitulated known variation in the activity of TF binding motifs across single GM12878 cells, as previously reported18,26 (Supplementary Fig. 3d).”

In the citing paper

“We found that chromatin accessibility from bulk ATAC-seq8 and DNase-seq2 and the aggregate chromatin accessibility across the different single-cell technologies18,19,24,25 were highly correlated (Fig. 1c,d).”