The advent of single-cell sequencing technologies has shifted cancer research to a new paradigm and revolutionized our understanding of cancer evolution, tumor heterogeneity, and the tumor microenvironment. Conventional genomic, transcriptomic, and epigenomic sequencing protocols require microgram-level input materials, and so cancer-related genomic studies were largely limited to bulk tumor sequencing, which does not address intratumor heterogeneity and complexity. ĭetailed understanding of tumor ecosystems at single-cell resolution has been limited for technological reasons. Cancer is increasingly viewed as a ‘tumor ecosystem’, a community in which tumor cells cooperate with other tumor cells and host cells in their microenvironment, and can also adapt and evolve to changing conditions. Cancer cells can also manifest resistance to various therapeutic drugs through cellular heterogeneity and plasticity. During oncogenesis, different populations of cancer cells that are genetically heterogeneous emerge, evolve, and interact with cells in the tumor microenvironment, which leads to host metabolism hijacking, immune evasion, metastasis to other body parts, and eventual mortality. Cancer, a disease caused by somatic mutations conferring uncontrolled proliferation and invasiveness, could in particular benefit from advances in single-cell analysis. Dissecting the composition and characterizing the interaction, dynamics, and function at the single-cell resolution are crucial for fully understanding the biology of almost all life phenomena, under both normal and diseased conditions.

A single cell is the ultimate unit of life activity, in which genetic mechanisms and the cellular environment interplay with each other and shape the formation and function of such complex structures as tissues and organs.

Limitations by JD Riggs