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Uterine Organoids Reveal Insights into Epithelial Specification and Plasticity in Development and Disease

ABSTRACT: Epithelial differentiation in the female reproductive tract (FRT) is essential for reproductive health, yet the mechanisms that govern epithelial fate specification remain poorly understood. At birth, FRT epithelium exhibits significant developmental plasticity, allowing differentiation into various epithelial subtypes. However, the regulatory pathways driving these early fate decisions, particularly in the uterus, are largely uncharacterized. Here, we employ neonatal mouse endometrial epithelial organoids and assembloid co-culture models to investigate how intrinsic cellular plasticity and mesenchymal signals influence uterine epithelial differentiation. We demonstrate that uterine epithelium undergoes marked age-dependent changes, shifting from a highly plastic state capable of differentiating into both monolayered and multilayered structures to a more restricted fate as development progresses. Interestingly, parallels between the developmental plasticity of neonatal uterine epithelium and pathological conditions such as endometrial cancer emerged, where similar regulatory mechanisms may be reactivated, driving abnormal epithelial differentiation and tumorigenesis. These findings provide new insights into the regulatory networks that guide early development and highlight how disruptions in these processes can contribute to disease, offering a valuable model for studying both normal uterine development and cancer progression.

ORGANISM(S): Mus musculus

PROVIDER: GSE278635 | GEO | 2025/01/01

REPOSITORIES: GEO

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