Cancer biology deciphered by single-cell transcriptomic sequencing

Abstract

Tumors are complex ecosystems in which heterogeneous cancer cells interact with their microenvironment composed of diverse immune, endothelial, and stromal cells. Cancer biology had been studied using bulk genomic and gene expression profiling, which however mask the cellular diversity and average the variability among individual molecular programs. Recent advances in single-cell transcriptomic sequencing have enabled a detailed dissection of tumor ecosystems and promoted our understanding of tumorigenesis at single-cell resolution. In the present review, we discuss the main topics of recent cancer studies that have implemented single-cell RNA sequencing (scRNA-seq). To study cancer cells, scRNA-seq has provided novel insights into the cancer stem-cell model, treatment resistance, and cancer metastasis. To study the tumor microenvironment, scRNA-seq has portrayed the diverse cell types and complex cellular states of both immune and non-immune cells interacting with cancer cells, with the promise to discover novel targets for future immunotherapy.

Keywords: cancer; single-cell transcriptomic sequencing; tumor microenvironment.

Figure 1

Intricate tumor ecosystem and the workflow for scRNA-seq analysis of tumors. (A) Tumors are complex ecosystems (left) composed of diverse malignant and nonmalignant cells (right). Nonmalignant cells include immune, endothelial, and stromal cells. Intra-tumor heterogeneity is an inherent feature of malignant cells mainly contributed by genetic heterogeneity and functional expression programs. These complicated cancer ecosystems underlie many critical facets of tumor biology. (B) Tumors are digested and sorted into single live cells and then profiled by scRNA-seq. Copy number variation (CNV) inference and canonical makers are used to annotate cell types. Cell states within each cell-type cluster are identified by bioinformatics clustering and functional programs. Advances in scRNA-seq have enabled a detailed dissection of tumor entities and enhanced our understanding of the underlying mechanisms at the resolution of individual cells

Figure 2

Emerging directions of cancer studies and development of scRNA-seq technologies