Application of Single-Cell Multi-Omics in Dissecting Cancer Cell Plasticity and Tumor Heterogeneity

Deshui Jia,Deshen Pan

doi:10.3389/fmolb.2021.757024

Abstract

Tumor heterogeneity, a hallmark of cancer, impairs the efficacy of cancer therapy and drives tumor progression. Exploring inter- and intra-tumoral heterogeneity not only provides insights into tumor development and progression, but also guides the design of personalized therapies. Previously, high-throughput sequencing techniques have been used to investigate the heterogeneity of tumor ecosystems. However, they could not provide a high-resolution landscape of cellular components in tumor ecosystem. Recently, advance in single-cell technologies has provided an unprecedented resolution to uncover the intra-tumoral heterogeneity by profiling the transcriptomes, genomes, proteomes and epigenomes of the cellular components and also their spatial distribution, which greatly accelerated the process of basic and translational cancer research. Importantly, it has been demonstrated that some cancer cells are able to transit between different states in order to adapt to the changing tumor microenvironment, which led to increased cellular plasticity and tumor heterogeneity. Understanding the molecular mechanisms driving cancer cell plasticity is critical for developing precision therapies. In this review, we summarize the recent progress in dissecting the cancer cell plasticity and tumor heterogeneity by use of single-cell multi-omics techniques.

Highlights

Tumor heterogeneity, including genetic heterogeneity, epigenetic heterogeneity, phenotypic and functional heterogeneity, plays essential roles in tumor progression, especially in promoting resistance to treatment and driving metastasis (Giraudeau et al, 2019; Guo et al, 2019; Hinohara and Polyak, 2019)
We summarize the recent progress in dissecting the cancer cell plasticity and tumor heterogeneity through single-cell multiomics techniques, including the scRNA-seq, Single-Cell DNA Sequencing, single-cell proteomics and single-cell epigenomics (Figure 1)
These findings indicate that single-cell epigenomics have advantages to exploring tumor heterogeneity and identifying mechanisms underlying cancer cells evolution

Summary

INTRODUCTION

Tumor heterogeneity, including genetic heterogeneity, epigenetic heterogeneity, phenotypic and functional heterogeneity, plays essential roles in tumor progression, especially in promoting resistance to treatment and driving metastasis (Giraudeau et al, 2019; Guo et al, 2019; Hinohara and Polyak, 2019). Dynamic evolution of cancer cells in a mouse model of lung adenocarcinoma has been investigated by scATAC-seq, which revealed an epigenetic continuum of cancer progression, characterized by loss of cellular identify and progression to a metastatic state (LaFave et al, 2020) Together, these findings indicate that single-cell epigenomics have advantages to exploring tumor heterogeneity and identifying mechanisms underlying cancer cells evolution. The subpopulations of ECs in tumors and their changes in gene expression following antiangiogenic treatment were analyzed by scRNA-seq (Zhao et al, 2018) Together, these studies demonstrated that single-cell technology greatly accelerates the understanding of stromal heterogeneity, providing new avenues to target these cellular components for precision cancer therapy. Single-cell technologies have shown great advantages in personalized therapy and prognosis prediction

LIMITATIONS

Findings

CONCLUSIONS