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The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation.

Original publication

DOI

10.1038/srep03545

Type

Journal article

Journal

Scientific Reports

Publication Date

18/12/2013

Volume

3

Addresses

Institute of Bioengineering and School of Engineering and Materials Science, Queen Mary University of London, Bancroft Road, Mile End, London E1 4NS, UK.

Keywords

Bone Marrow Cells, Cells, Cultured, Cilia, Humans, Amides, Pyridines, Myosins, Tumor Suppressor Proteins, RNA, Small Interfering, Enzyme Inhibitors, Cell Culture Techniques, Mechanotransduction, Cellular, Cell Differentiation, Cell Proliferation, RNA Interference, Surface Properties, beta Catenin, rho-Associated Kinases, Stress, Physiological, Actin Cytoskeleton, Wnt3A Protein, Axin Protein, Wnt Signaling Pathway, Mesenchymal Stromal Cells