Authors: Pratyusha Bala, Jonathan P. Rennhack, Daulet Aitymbayev, Clare Morris, Sydney M. Moyer, Gina N. Duronio, Paul Doan, Zhixin Li, Xiaoyan Liang, Jason L. Hornick, Matthew B. Yurgelun, William C. Hahn, Nilay S. Sethi
Published: 2023-04-10
Source: Full article
Cell state plasticity is carefully regulated in adult epithelia to prevent cancer. The aberrant expansion of the normally restricted capability for cell state plasticity in neoplasia is poorly defined. Using genetically engineered and carcinogen-induced mouse models of intestinal neoplasia, we observed that impaired differentiation is a conserved event preceding cancer development. Single-cell RNA sequencing (scRNA-seq) of premalignant lesions from mouse models and a patient with hereditary polyposis revealed that cancer initiates by adopting an aberrant transcriptional state characterized by regenerative activity, marked by