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M. Casado-Pelaez, A. Bueno-Costa, M. Esteller
Single cell cancer epigenetics
Trends in Cancer9 Jul 2022, .
The epigenome encompasses several mechanisms controlling gene expression that can be aberrantly regulated during cancer development and progression. Tumors are highly complex and heterogeneous biological systems that require the study of epigenetic alterations at a single cell resolution.
Several single cell technologies developed to study different layers of the epigenome, such as chromatin accessibility or histone modifications, have been developed and applied in cancer research over the past few years, improving our understanding of the mechanisms driving tumorigenesis.
Although these techniques are promising, most are still nascent and present limitations, such as low throughput and limited coverage. In addition, the analysis and integration of the various single cell epigenomic data modalities have challenges and require the development of new computational tools.
Bulk sequencing methodologies have allowed us to make great progress in cancer research. Unfortunately, these techniques lack the resolution to fully unravel the epigenetic mechanisms that govern tumor heterogeneity. Consequently, many novel single cell-sequencing methodologies have been developed over the past decade, allowing us to explore the epigenetic components that regulate different aspects of cancer heterogeneity, namely: clonal heterogeneity, tumor microenvironment (TME), spatial organization, intratumoral differentiation programs, metastasis, and resistance mechanisms. In this review, we explore the different sequencing techniques that enable researchers to study different aspects of epigenetics (DNA methylation, chromatin accessibility, histone modifications, DNA–protein interactions, and chromatin 3D architecture) at the single cell level, their potential applications in cancer, and their current technical limitations.