Cancer cell states: Lessons from ten years of single-cell RNA-sequencing of human tumors

Human tumors are intricate ecosystems composed of diverse genetic clones and malignant cell states that evolve in a complex tumor micro-environment. Single-cell RNA-sequencing (scRNA-seq) provides a compelling strategy to dissect this intricate biology and has enabled a revolution in our ability to understand tumor biology over the last ten years. Here we reflect on this first decade of scRNA-seq in human tumors and highlight some of the powerful insights gleaned from these studies. We first focus on computational approaches for robustly defining cancer cell states and their diversity and highlight some of the most common patterns of gene expression intra-tumor heterogeneity (eITH) observed across cancer types. We then discuss ambiguities in the field in defining and naming such eITH programs. Finally, we highlight critical developments that will facilitate future research and the broader implementation of these technologies in clinical settings.

Itay Tirosh,¹ Mario L Suva²

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel. Electronic address: .
Department of Pathology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: .

Source: Itay Tirosh, Mario L Suva. Cancer cell states: Lessons from ten years of single-cell RNA-sequencing of human tumors. Cancer Cell. 2024 Sep 9;42(9):1497-1506. doi: 10.1016/j.ccell.2024.08.005.

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