Open AccessGenomic signatures of the unjamming transition in compressed human bronchial epithelial cells
Author(s) -
Margherita De Marzio,
Ayşe Kılıç,
Enrico Maiorino,
Joseph F. Mitchel,
Chimwemwe Mwase,
Michael J. O’Sullivan,
Maureen McGill,
Robert Chase,
Jeffrey J. Fredberg,
JinAh Park,
Kimberly Glass,
Scott T. Weiss
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abf1088
Subject(s) - extracellular matrix , microbiology and biotechnology , bronchoconstriction , integrin , actin , motility , biology , signal transduction , mapk/erk pathway , rna , chemistry , cell , gene , genetics , immunology , asthma
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.