Bulletin of the American Physical Society
2023 APS March Meeting
Volume 68, Number 3
Las Vegas, Nevada (March 5-10)
Virtual (March 20-22); Time Zone: Pacific Time
Session N10: Cell Fate Transitions
11:30 AM–2:30 PM,
Wednesday, March 8, 2023
Room: Room 202
Sponsoring
Unit:
DBIO
Chair: Jianhua Xing, University of Pittsburgh; Sahand Rahi, Ecole Polytechnique Federale de Lausanne
Abstract: N10.00001 : 3D genome organization in the epithelial-mesenchymal transition spectrum
11:30 AM–12:06 PM
Presenter:
Ruby Huang
(National Taiwan University)
Author:
Ruby Huang
(National Taiwan University)
We perform Hi-C analysis and combine ChIP-seq data across cancer cell lines representing different EMT states. We demonstrate that the epithelial and mesenchymal genes are regulated distinctively. We find that EMT genes are regulated within their topologically associated domains (TADs), with only a subset of mesenchymal genes being influenced by A/B compartment switches, indicating topological remodeling is required in the transcriptional regulation of these genes. At the TAD level, epithelial and mesenchymal genes are associated with different regulatory trajectories. The epithelial gene-residing TADs are enriched with H3K27me3 marks in the mesenchymal-like states. The mesenchymal gene-residing TADs, which do not show enrichment of H3K27me3 in epithelial-like states, exhibit increased interaction frequencies with regulatory elements in the mesenchymal-like states.
We propose a novel workflow coupling immunofluorescence and dielectrophoresis to unravel EMT heterogeneity at single-cell resolution. The predicted three-dimensional structures of chromosome 10, harboring Vimentin, identify cell clusters of different states. Our results pioneer a novel avenue to decipher the complexities underlying the regulation of EMT and may infer the barriers of plasticity in the 3D genome context.
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