Cellular mechano-environment regulates the mammary circadian clock

Nan Yang, Jack Williams, Vanja Pekovic-Vaughan, Pengbo Wang, Safiah Olabi, James McConnell, Nicole Gossan, Alun Hughes, Julia Cheung, Charles H Streuli, Qing-Jun Meng

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)14287
JournalNature Communications
Publication statusPublished - 30 Jan 2017


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