Primary cilia, tiny hair-like structures protruding from a cell, may serve as signaling hubs, influencing a number of biochemical pathways including those involved in stem cell differentiation. Cilia are also sensitive to their surroundings. Working on a hunch that cilia, under the influence of different surface topographies, could alter their signaling patterns, scientists at Queen Mary University of London tried growing mesenchymal stem cells (MSCs) on micro-grooved surfaces. These scientists found that the growth conditions they imposed disrupted the biochemical pathway that determines the length of the primary cilia. In addition, the change in length of the structure ultimately controlled the subsequent behavior of the stem cells.
The scientists published their results December 18 in Scientific Reports, in a paper entitled “Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells.” In this paper, the scientists noted that MSCs cultured on grooves “expressed elongated primary cilia, through reduced actin organization.”
The scientists also described how they evaluated the role of the primary cilium, particularly cilia assembly, in regulating canonical wnt signaling: “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.”
These results, say the scientists, indicate that both positive and negative regulation of cilia assembly can finely tune MSC responsiveness to wnt stimulation in opposing directions. It is likely, they add, that topography-induced changes in cilia structure may regulate these pathways, which also have an involvement in stem cell differentiation.
Altering topographical cues appears to vary cytoskeletal tension, leading to alterations in primary cilia structure, which provides a way to regulate wnt responsiveness, highlighting the possibility of manipulating wnt signaling and associated stem cell differentiation.
This finding may be applied in the development of new therapies for a range of medical treatments where scientists aim to replace or regenerate tissues that have become diseased or dysfunctional. “This may be achieved,” wrote the authors, “using biomaterials incorporating topographical cues or direct pharmaceutical intervention.”
“Primary cilia are a thousand times smaller than the width of a human hair and are a ubiquitous feature of most cell types but were once thought to be irrelevant. However, our research shows that they play a key role in stem cell differentiation,” concluded Martin Knight, Ph.D., a study co-author and a professor of mechanobiology at Queen Mary’s School of Engineering and Materials Science and a director at the Institute of Bioengineering.