Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features

To uncover gene regulatory principles underlying heterogeneous cancer cell states and their linked environmental features, here we present a pan-cancer single-cell, multi-omic atlas of human cancer cell lines, including a compendium of 240,957 transcriptomes and 223,347 chromatin-accessibility profiles from primary cancers spanning 20 tumor types.

We revealed extensive pan-cancer cell-state heterogeneity, core gene-regulatory networks, and consensus epithelial–mesenchymal transition (EMT) trajectories that transcend tissue of origin and are governed by conserved epigenomic and transcriptomic features. In addition, our copy-number variation analysis implicated transcription factor amplification, followed by hyperactive downstream regulation, as a major driver of malignant states.