Profiling Chromatin Accessibility at Single-Cell Resolution

Abstract

How distinct transcriptional programs are enacted to generate cellular heterogeneity and plasticity, and enable complex fate decisions are important open questions. One key regulator is the cell’s epigenome state that drives distinct transcriptional programs by regulating chromatin accessibility. Genome-wide chromatin accessibility measurements can impart insights into regulatory sequences (in)accessible to DNA-binding proteins at a single-cell resolution. This review outlines molecular methods and bioinformatic tools for capturing cell-to-cell chromatin variation using single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) in a scalable fashion. It also covers joint profiling of chromatin with transcriptome/proteome measurements, computational strategies to integrate multi-omic measurements, and predictive bioinformatic tools to infer chromatin accessibility from single-cell transcriptomic datasets. Methodological refinements that increase power for cell discovery through robust chromatin coverage and integrate measurements from multiple modalities will further expand our understanding of gene regulation during homeostasis and disease.

Single‐cell transcriptomics in human skin research: available technologies, technical considerations and disease applications

“…By combining transcriptomics with proteomics and epigenomics, scientists can elucidate regulatory elements and transcription factors that affect gene expression, methylation, protein abundance and chromatin accessibility. 84 The 10× platform enables the combination of scRNA-seq with other complementary technologies such as ATAC-seq, which uses a prokaryotic transposase to tag accessible regulatory regions with sequencing adaptors 85 or CITE-seq, 86 which measures cell surface protein levels by using oligonucleotide-labelled antibodies. 87 This method can be particularly useful in better characterizing cutaneous immune cell populations that participate in multiple inflammatory signalling pathways.…”

Optical Imaging of Epigenetic Modifications in Cancer: A Systematic Review

“…Because of the nature of epigenetic inheritance, the precise detection of DNA methylation, histone modifications, ncRNA regulation, and chromosome remodeling are important for epigenetics-related biological studies, as well as for cancer diagnosis, prognosis, and treatment. Conventional laborious techniques for epigenetic biomarker detection mainly include in vitro enzyme-coupled assays (Dorgan et al 2006;Kim et al 2000), antibody-based assays, chromatin immunoprecipitation (ChIP) (Park 2009), chromatin conformation capture (3C)-derived assays (Ethier et al 2012), assay for transposase-accessible chromatin using sequencing (Mezger et al 2018;Sinha et al 2021), radiometric assays (Bannister and Kouzarides 1996), and mass spectrometry (Licht and Jantsch 2016). Although these approaches are fast and hold high detection sensitivity and specificity, they are not close to clinical diagnosis.…”

Sparsely Connected Autoencoders: A Multi-Purpose Tool for Single Cell omics Analysis

“…Single cell RNAseq (scRNAseq) [ 1 , 2 ] allows the investigation of the transcriptome from individual cells, providing an extended view of cellular differences, which can deliver a better understanding of the function of each individual cell within its microenvironment. scRNAseq has opened the route to the development of other single-cell methods, which now enable the simultaneous measurement of other data modalities like scCITEseq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing), which allows the expression quantification of cell surface proteins [ 3 ]; scATACseq (Assay for Transposase-Accessible Chromatin using sequencing), which depicts accessible chromatin regions [ 4 ] and single cell spatial transcriptomics, which measures transcription expression directly on a tissue [ 5 ]. Since single cell omics analyses are becoming the most important way to investigate the functionality of healthy and disease tissues, grasping biological knowledge from single cell omics [ 6 , 7 ] is a mandatory subject.…”