Facial reconstruction

Search LJMU Research Online

Browse Repository | Browse E-Theses

Cellular mechano-environment regulates the mammary circadian clock

Yang, N, Williams, J, Pekovic-Vaughan, V, Wang, P, Olabi, S, McConnell, J, Gossan, N, Hughes, ATL, Cheung, J, Streuli, CH and Meng, Q-J (2017) Cellular mechano-environment regulates the mammary circadian clock. Nature Communications, 8. ISSN 2041-1723

Yang et al (Meng) (2017) Cellular mechano-environment regulates the mammary circadian clock.pdf - Published Version
Available under License Creative Commons Attribution.

Download (6MB) | Preview


Circadian clocks drive B24 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: MD Multidisciplinary
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QP Physiology
Divisions: Natural Sciences & Psychology (closed 31 Aug 19)
Publisher: Nature Publishing Group
Related URLs:
Date Deposited: 05 Apr 2018 10:12
Last Modified: 04 Sep 2021 10:36
DOI or ID number: 10.1038/ncomms14287
URI: https://researchonline.ljmu.ac.uk/id/eprint/8416
View Item View Item