Each tumour contains diverse cellular states that underlie intratumour heterogeneity (ITH), a central challenge of cancer therapeutics. Dozens of recent studies have begun to describe ITH by single-cell RNA sequencing, but each study typically profiled only a small number of tumours and provided a narrow view of transcriptional ITH. Here a team led by researchers at the Weizmann Institute of Science curate, annotate and integrate the data from 77 different studies to reveal the patterns of transcriptional ITH across 1,163 tumour samples covering 24 tumour types. Among the malignant cells, the researchers identify 41 consensus meta-programs, each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many tumours. The meta-programs cover diverse cellular processes including both generic (for example, cell cycle and stress) and lineage-specific patterns that the researchers map into 11 hallmarks of transcriptional ITH. Most meta-programs of carcinoma cells are similar to those identified in non-malignant epithelial cells, suggesting that a large fraction of malignant ITH programs are variable even before oncogenesis, reflecting the biology of their cell of origin. They further extended the meta-program analysis to six common non-malignant cell types and utilize these to map cell–cell interactions within the tumour microenvironment. In summary, these researchers have assembled a comprehensive pan-cancer single-cell RNA-sequencing dataset, which is available through the Curated Cancer Cell Atlas website, and leveraged this dataset to carry out a systematic characterization of transcriptional ITH.
Availability – https://www.weizmann.ac.il/sites/3CA/
Gavish A, Tyler M, Greenwald AC, Hoefflin R, Simkin D, Tschernichovsky R, Galili Darnell N, Somech E, Barbolin C, Antman T, Kovarsky D, Barrett T, Gonzalez Castro LN, Halder D, Chanoch-Myers R, Laffy J, Mints M, Wider A, Tal R, Spitzer A, Hara T, Raitses-Gurevich M, Stossel C, Golan T, Tirosh A, Suvà ML, Puram SV, Tirosh I. (2023) Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours. Nature [Epub ahead of print]. [abstract]
