Widespread transcriptional memory shapes heritable states and functional heterogeneity in cancer and stem cells [RNA-Seq]

However, single-cell snapshots lack temporal information to identify these states. We employ lineage-resolved single-cell transcriptomics to map heritable cell states that persist across divisions, distinguishing them from transient fluctuations.

We uncover that heritable states are underpinned by widespread transcriptional memory, whereby heritable gene expression defines two classes of states: clustered states, characterized by clustered gene expression, and latent states, marked by non-clustered gene expression. This memory shows conservation across cell types and conditions and appears to be maintained by robust epigenetic mechanisms resistant to environmental perturbations.