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.
细胞与细胞间不同的转录活动是影响细胞间的异质性、可塑性，并最终决定细胞命运。染色质结构（如：染色质的开放程度）在基因表达调控中起关键作用。全基因组范围的染色质开放程度检测可以使我们获得单细胞水平的调控蛋白结合区域。本文概述了用来揭示不同细胞之间染色质开放程度变化的实验技术——单细胞ATAC测序技术（scATAC-seq），以及相关的生物信息分析方法。同时，本文还囊括了对scATAC数据与转录组、蛋白质组等多组学数据整合分析的分析策略，以及如何使用单细胞转录组数据用于预测染色质开放程度的生物信息工具的介绍。通过更精细尺度的染色质覆盖以及整合多组学信息，我们可以更深入的理解稳态和疾病中的基因转录调控活动。





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