Combinatorial perturbation analysis reveals divergent regulations of mesenchymal genes during epithelial-to-mesenchymal transition

NPJ Systems Biology and Applications
K. WatanabeTian Hong

Abstract

Epithelial-to-mesenchymal transition (EMT), a fundamental transdifferentiation process in development, produces diverse phenotypes in different physiological or pathological conditions. Many genes involved in EMT have been identified to date, but mechanisms contributing to the phenotypic diversity and those governing the coupling between the dynamics of epithelial (E) genes and that of the mesenchymal (M) genes are unclear. In this study, we employed combinatorial perturbations to mammary epithelial cells to induce a series of EMT phenotypes by manipulating two essential EMT-inducing elements, namely TGF-β and ZEB1. By measuring transcriptional changes in more than 700 E-genes and M-genes, we discovered that the M-genes exhibit a significant diversity in their dependency to these regulatory elements and identified three groups of M-genes that are controlled by different regulatory circuits. Notably, functional differences were detected among the M-gene clusters in motility regulation and in survival of breast cancer patients. We computationally predicted and experimentally confirmed that the reciprocity and reversibility of EMT are jointly regulated by ZEB1. Our integrative analysis reveals the key roles of ZEB1 in coordinating...Continue Reading

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Citations

Oct 15, 2020·Journal of the Royal Society, Interface·Daner A SilveiraJosé Carlos M Mombach
Feb 4, 2021·Journal of Clinical Medicine·Adithya ChedereMohit Kumar Jolly
Apr 9, 2020·Frontiers in Bioengineering and Biotechnology·Priyanka ChakrabortyMohit Kumar Jolly
Apr 9, 2020·Frontiers in Molecular Biosciences·Stanislav DrápelaKarel Souček
Apr 4, 2021·Cancers·Yelyzaveta ShlyakhtinaMaximiliano M Portal
May 21, 2021·Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada·Shreyas U HirwaySeth H Weinberg

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Methods Mentioned

BETA
PCA
FACS
PCR
flow cytometry

Software Mentioned

Plotter
Fiji
mathop
TrackMate
KM
R
IncuCyte
EdgeR
SOM
FACS DiVa6

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