Single-nucleus RNA sequencing of human trophoblast organoids and endometrial organoids co-culture model

Here, we performed single-nucleus RNA sequencing of hEMO mono-culture, hTOr mono-culture, and their co-culture to dissect the transcriptomic landscape of this interaction. Our analysis reveals that hTOr-derived signals drive a metabolic and secretory activation in the endometrial epithelium.

We identified a unique 'Activated' hEMO population emerging specifically upon co-culture, distinct from the LGR5+ homeostatic state. This transition was characterized by a robust upregulation of oxidative phosphorylation and glycolysis, concurrent with sustained proliferation, demonstrating that the trophoblast actively reprograms the endometrium into a hyper-metabolic state.