Transcriptional signals of dedifferentiation in human cancer

Abstract

As normal cells transform into cancers, their cell state changes (or "dedifferentiates"), which may drive cancer cells into a stem-like or more primordial, foetal or embryonic cell state. Here, we used single cell atlases to study dedifferentiation in transcriptional terms across a wide spectrum of adult and childhood cancers. At the level of the whole transcriptome, we find that adult cancers rarely return to an embryonic state, but rather that a foetal state is a near-universal feature of childhood cancers. We extend these bulk transcriptomic findings to a single cell resolution analysis of colorectal and liver cancers, confirming the lack of reversion to a primordial state in adult tumours and the retention of foetal signals in childhood cancers. Our findings provide a nuanced picture of dedifferentiation in these two groups of neoplasms, indicating cancer-specific rather than universal patterns of dedifferentiation pervade adult epithelial cancers.