An international study led by a University of Ottawa Faculty of Medicine investigator reveals that the tiny hair-like structures that extend from the surface of neighboring cells play a critical role in controlling the behavior of adult neural stem cells.
This discovery could redefine our understanding of how stem cells are regulated in living tissues across the body. It provides compelling evidence that stem cell niches are not governed solely by biochemical signals, but also by physical forces generated by nearby cells.
Ultimately, the findings unlocking how microscopic forces generated by the action of cells’ hair-like ‘cilia’ shape the fate of stem cells opens promising new possibilities for regenerative medicine and the creation of novel treatments.
Published in the journal Neuron, the collaborative work was led by Dr. Armen Saghatelyan, professor in the uOttawa Faculty’s Department of Cellular and Molecular Medicine, with research colleagues based in Germany and Canada.
Unlocking cellular secrets
With Dr. Saghatelyan at the helm, the research team focused on neural stem cells located in the brain’s subventricular zone, where they are surrounded by other specialized cells arranged in a distinctive pinwheel-shaped structure.
“This study demonstrates that stem cell activation and proliferation is not only controlled by molecular factors but also by mechanical stimuli.”
Dr. Armen Saghatelyan
Dubbed ‘ependymal’ cells, these specialized cells line the brain’s fluid-filled ventricles. The rhythmic beating of their cilia circulates cerebrospinal fluid through the brain.
The team of collaborators aimed to demonstrate that the mechanical force of these cells’ pulsing cilia act as a kind of biological signal that ultimately maintains stem cell dormancy.
To investigate this phenomenon, researchers developed an innovative and highly precise technique to temporarily stop cilia movement in living brains.
Using an external magnetic field combined with tiny magnetic beads coupled to antibodies targeting the cilia of ependymal’ cells, the team could inhibit cilia movement without damaging surrounding tissue. The technical hurdles were substantial.
“The development of this approach required a lot of troubleshooting and testing of various systems,” says Dr. Saghatelyan, adding that the biggest challenge was advancing technologies simultaneously. “On one hand, we needed to monitor cilia beating with high spatial and temporal resolution in brain tissue, and on the other hand, modulate cilia beating using magnetic fields.”
Waking up neural stem cells
The results of their experiments were immediate and striking: within hours of halting cilia beating, dormant neural stem cells roused from their slumber and became activated.
“While we developed and used this approach for ependymal cell lining the walls of brain ventricles, it can also be used for various other cilia-bearing cells present in distinct organs.”
Dr. Saghatelyan
“This study demonstrates that stem cell activation and proliferation is not only controlled by molecular factors but also by mechanical stimuli,” Dr. Saghatelyan explains.
Beyond the brain
The team’s discovery could have broader implications for stem cell biology throughout the body.
Their novel approach makes it potentially possible to modulate cilia beating in cells found in organs including the lungs, kidneys, and gut.
“While we developed and used this approach for ependymal cell lining the walls of brain ventricles, it can also be used for various other cilia-bearing cells present in distinct organs,” he explains, suggesting that mechanical regulation of stem cells may be a kind of universal biological principle.