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Genomic signatures of the unjamming transition in compressed human bronchial epithelial cells

Authors :
Scott T. Weiss
Jennifer A. Mitchel
Chimwemwe Mwase
Jin-Ah Park
Robert P. Chase
Kimberly Glass
Michael O'Sullivan
Enrico Maiorino
Maureen McGill
Ayşe Kılıç
Margherita De Marzio
Jeffrey J. Fredberg
Source :
Science Advances
Publication Year :
2021
Publisher :
American Association for the Advancement of Science (AAAS), 2021.

Abstract

Temporal RNA-seq data reveal genomic signatures of the unjamming transition in compressed human bronchial epithelial cells.<br />Epithelial tissue can transition from a jammed, solid-like, quiescent phase to an unjammed, fluid-like, migratory phase, but the underlying molecular events of the unjamming transition (UJT) remain largely unexplored. Using primary human bronchial epithelial cells (HBECs) and one well-defined trigger of the UJT, compression mimicking the mechanical effects of bronchoconstriction, here, we combine RNA sequencing data with protein-protein interaction networks to provide the first genome-wide analysis of the UJT. Our results show that compression induces an early transcriptional activation of the membrane and actomyosin network and a delayed activation of the extracellular matrix (ECM) and cell-matrix networks. This response is associated with a signaling cascade that promotes actin polymerization and cellular motility through the coordinated interplay of downstream pathways including ERK, JNK, integrin signaling, and energy metabolism. Moreover, in nonasthmatic versus asthmatic HBECs, common genomic patterns associated with ECM remodeling suggest a molecular connection between airway remodeling, bronchoconstriction, and the UJT.

Details

ISSN :
23752548
Volume :
7
Database :
OpenAIRE
Journal :
Science Advances
Accession number :
edsair.doi.dedup.....c38e1e90eae673c3d1c3f0fe3fbed8c5