Phenomics Demonstrates Cytokines Additive Induction of Epithelial to Mesenchymal Transition

J Cell Physiol. 2024 Nov 20. doi: 10.1002/jcp.31491. Online ahead of print.

Abstract

Epithelial to mesenchymal transition (EMT) is highly plastic with a programme where cells lose adhesion and become more motile. EMT heterogeneity is one of the factors for disease progression and chemoresistance in cancer. Omics characterisations are costly and challenging to use. We developed single cell phenomics with easy to use wide-field fluorescence microscopy. We analyse over 70,000 cells and combined 53 features. Our simplistic pipeline allows efficient tracking of EMT plasticity, with a single statistical metric. We discriminate four high EMT plasticity cancer cell lines along the EMT spectrum. We test two cytokines, inducing EMT in all cell lines, alone or in combination. The single cell EMT metrics demonstrate the additive effect of cytokines combination on EMT independently of cell line EMT spectrum. The effects of cytokines are also observed at the front of migration during wound healing assay. Single cell phenomics is uniquely suited to characterise the cellular heterogeneity in response to complex microenvironment and show potential for drug testing assays.

Keywords: cancer; cytokines; epithelial‐to‐mesenchymal transition; fluorescence microscopy; phenomics.