Comparative single-cell transcriptomes of dose and time dependent epithelial-mesenchymal spectrums

Area of Science:

• Cell Biology
• Genomics
• Cancer Research

Background:

• Epithelial-mesenchymal transition (EMT) is crucial for development and disease, with intermediate states observed in tumors.
• Previous in vitro studies on EMT used single doses, leaving uncertainty about stable intermediate states in transcriptomes.

Purpose of the Study:

• To investigate if dose-dependent signaling creates stable intermediate states in EMT using single-cell RNA-sequencing.
• To compare dose-dependent and time-dependent EMT transcriptomes for enhanced gene detection and understanding of cellular states.

Main Methods:

• Human mammary epithelial cells were treated with multiple doses of TGF-β.
• Single-cell RNA-sequencing was performed to analyze transcriptomic profiles.
• Dose- and time-dependent EMT transcriptomes were compared.

Main Results:

• Dose-dependent EMT was found to harbor multiple intermediate states at near steady state.
• Dose-dependent data showed higher sensitivity in detecting EMT-associated genes compared to time-dependent data.
• Unique cell clusters were identified in time-dependent EMT, representing cells transitioning to stable states.

Conclusions:

• A stable EMT continuum exists at single-cell resolution, revealed by dose-dependent signaling.
• Combining dose- and time-dependent analyses provides complementary information and enables accurate cancer patient prognosis.