Cell state dynamics during early stages of serous endometrial carcinoma.

Abstract

Serous endometrial carcinoma (SEC) is one of the most lethal types of uterine cancer, responsible for about 40% of all endometrial cancer-related deaths. Cell state dynamics during the early stages of SEC remain largely unknown, thereby hindering early detection and treatment of this disease. Here, we provide a comprehensive census of cell types and their states for normal, predysplastic, and dysplastic endometrium in a genetic mouse model of SEC. We report that predysplastic changes are characterized by increasingly diverse immature luminal epithelial cell populations. The decrease in differentiated cell states is accompanied by the emergence of a 'single-cell and spatial transcriptome dysregulation' gene signature. This signature contains seven genes that predict poor patient prognosis and are promising diagnostic markers and therapeutic targets. In summary, our results suggest an important role of the luminal epithelial cell state in SEC pathogenesis and validate our mouse SEC model as a capable comparative platform for preclinical studies. © 2025 The Pathological Society of Great Britain and Ireland.