Quantifying epigenetic reprogramming and cellular plasticity in preneoplastic lesions reveals dedifferentiation as a key precancer hallmark

PLASTIC quantifies cellular plasticity and epigenetic reprogramming from single-cell RNA-seq, revealing a high cancer risk state marked by increased dedifferentiation in pan-preneoplastic tissue.

• Why it matters: Epigenetic reprogramming and plasticity raise carcinogenic transformation risk, but measuring these properties in single cells across tissues remains a key challenge.
• What they did: The study develops and validates PLASTIC, a pan-tissue computational framework that builds Waddington-like landscapes from single-cell RNA-seq to identify high cancer risk states.
• The result: In pan-preneoplastic tissue, epigenetic reprogramming correlates with cellular plasticity and cancer-risk, and PLASTIC predicts metaplasia emergence in normal lung cells from smokers, validated in independent data.