Epithelial and stromal circadian clocks are inversely regulated by their mechanomatrix environment

Jack Williams, Nan Yang, Amber Wood, Egor Zindy, Qing-Jun Meng, Charles Streuli

Research output: Contribution to journalArticlepeer-review


The circadian clock is an autonomous molecular feedback loop inside almost every cell in the body. We have shown that the mammary epithelial circadian clock is regulated by the cellular microenvironment. Moreover, a stiff extracellular matrix dampens the oscillations of the epithelial molecular clock. Here, we extend this analysis to other tissues and cell types, and identify an inverse relationship between circadian clocks in epithelia and fibroblasts.
Epithelial cells from mammary gland, lung and skin have significantly stronger oscillations of clock genes in soft 3D microenvironments, compared to stiff 2D environments. Fibroblasts isolated from the same tissues show the opposite response, exhibiting stronger oscillations and more prolonged rhythmicity in stiff microenvironments. RNA analysis identified that a subset of mammary epithelial clock genes, and their regulators, are upregulated in 3D microenvironments in soft compared to stiff gels. Furthermore, the same genes are inversely regulated in fibroblasts isolated from the same tissues. Thus, our data reveal for the first time an intrinsic difference in the regulation of circadian genes in epithelia and fibroblasts.
Original languageEnglish
JournalJournal of Cell Science
Publication statusPublished - 6 Mar 2018

Research Beacons, Institutes and Platforms

  • Manchester Institute for Collaborative Research on Ageing


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