以前的研究传统上将癌细胞的起始归因于基因突变，认为它们是致癌的基本驱动因素。然而，最近的研究揭示了表观基因组改变在肿瘤微环境中存在的各种细胞类型中的关键作用，表明它们对肿瘤形成和进展的潜在贡献。尽管有这些重要的发现，但由于缺乏适当的技术工具和方法，在过去几年中理解调节肿瘤异质性的表观遗传机制的进展一直受到阻碍。单细胞测序的出现增强了我们对调控肿瘤异质性的表观遗传机制的理解。通过揭示单个细胞的不同表观遗传层（染色质可及性、DNA/RNA甲基化、组蛋白修饰、核小体定位）和单细胞水平的不同组学（转录组学、基因组学、多组学）来研究肿瘤异质性。这些技术为我们提供了对肿瘤内异质性的分子基础的新见解，并有助于揭示肿瘤发展中的关键分子事件和驱动机制。本文对各种组学中单细胞测序的新兴分析和实验方法进行了全面综述，重点关注特别是表观基因组学。这些方法有可能捕获和整合单个癌细胞的多个维度，从而揭示肿瘤异质性和表观遗传特征。此外，本文还概述了这些技术的未来趋势及其当前的技术局限性。© 2023。BioMed Central Ltd.，Springer Nature 旗下公司。

Previous studies have traditionally attributed the initiation of cancer cells to genetic mutations, considering them as the fundamental drivers of carcinogenesis. However, recent research has shed light on the crucial role of epigenomic alterations in various cell types present within the tumor microenvironment, suggesting their potential contribution to tumor formation and progression. Despite these significant findings, the progress in understanding the epigenetic mechanisms regulating tumor heterogeneity has been impeded over the past few years due to the lack of appropriate technical tools and methodologies.The emergence of single-cell sequencing has enhanced our understanding of the epigenetic mechanisms governing tumor heterogeneity by revealing the distinct epigenetic layers of individual cells (chromatin accessibility, DNA/RNA methylation, histone modifications, nucleosome localization) and the diverse omics (transcriptomics, genomics, multi-omics) at the single-cell level. These technologies provide us with new insights into the molecular basis of intratumoral heterogeneity and help uncover key molecular events and driving mechanisms in tumor development.This paper provides a comprehensive review of the emerging analytical and experimental approaches of single-cell sequencing in various omics, focusing specifically on epigenomics. These approaches have the potential to capture and integrate multiple dimensions of individual cancer cells, thereby revealing tumor heterogeneity and epigenetic features. Additionally, this paper outlines the future trends of these technologies and their current technical limitations.© 2023. BioMed Central Ltd., part of Springer Nature.