Cellular mechano-environment regulates the mammary circadian clock

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Yang, Nan, Williams, Jack, Pekovic-Vaughan, Vanja ORCID: 0000-0002-7876-652X, Wang, Pengbo, Olabi, Safiah, McConnell, James, Gossan, Nicole, Hughes, Alun, Cheung, Julia, Streuli, Charles H et al (show 1 more authors) and Meng, Qing-Jun (2017) Cellular mechano-environment regulates the mammary circadian clock. Nature Communications, 8 (1). 14287-.

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Official URL: https://www.nature.com/articles/ncomms14287

Abstract

Circadian clocks drive ∼24 h rhythms in tissue physiology. They rely on transcriptional/translational feedback loops driven by interacting networks of clock complexes. However, little is known about how cell-intrinsic circadian clocks sense and respond to their microenvironment. Here, we reveal that the breast epithelial clock is regulated by the mechano-chemical stiffness of the cellular microenvironment in primary cell culture. Moreover, the mammary clock is controlled by the periductal extracellular matrix in vivo, which contributes to a dampened circadian rhythm during ageing. Mechanistically, the tension sensing cell-matrix adhesion molecule, vinculin, and the Rho/ROCK pathway, which transduces signals provided by extracellular stiffness into cells, regulate the activity of the core circadian clock complex. We also show that genetic perturbation, or age-associated disruption of self-sustained clocks, compromises the self-renewal capacity of mammary epithelia. Thus, circadian clocks are mechano-sensitive, providing a potential mechanism to explain how ageing influences their amplitude and function.

Item Type:	Article
Uncontrolled Keywords:	Breast, Epithelium, Spheroids, Cellular, Extracellular Matrix, Epithelial Cells, Animals, Mice, Inbred C57BL, Mice, Transgenic, Humans, Mice, Breast Diseases, Amides, Pyridines, Vinculin, RNA, Small Interfering, Tissue Culture Techniques, Signal Transduction, Circadian Rhythm, Aging, Female, rho-Associated Kinases, CLOCK Proteins, HEK293 Cells, Circadian Clocks, Primary Cell Culture, Cellular Microenvironment, Cell Self Renewal
Depositing User:	Symplectic Admin
Date Deposited:	30 Aug 2017 15:04
Last Modified:	19 Jan 2023 06:56
DOI:	10.1038/ncomms14287
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3009243