Stem cells respond to mechanical forces by changing their structure The actin cytoskeleton (in green) is able to remodel and strengthen in response to strain. As the cytoskeleton is directly linked to the nucleus and thereby to DNA (in blue), mechanical forces are transmitted onto DNA, changing its structural organization and gene expression. Picture by Huy Quang Le, University of Cologne
Researchers from the University of Cologne, Germany, have identified how mechanical stimuli cause stem cells in the skin to change their gene expression and thereby the differentiation of their daughter cells, according to a paper published online ahead of print in Nature Cell Biology (July 11, 2016).
“Our skin protects us against the outside world while being constantly exposed to toxic insults, injuries, UV radiation and mechanical strain. Therefore it is particularly important for skin cells to be able to respond to forces,” said Huy Quang Le, a doctoral student at the University and lead author on the study, in a press release.
The investigators used a special mechanical device to expose skin stem cell cultures to similar mechanical stretch that they would experience inside normal tissue. Gene expression analysis of the stretched samples showed thousands of genes were downregulated, with only a few upregulated.
Further research found that stretching the samples induced global changes in how DNA was packed within the nucleus of the sample cells, resulting in a widespread repression of the transcription of genetic information into proteins. Since many specialized proteins are needed as part of stem cell differentiation, this meant that stretching the samples prevented the stem cells from differentiating when they were exposed to a signal that would normally trigger differentiation.
Senior author Dr. Sara Wickström, principal investigator at the Max Planck Institute for Biology of Ageing at the Universityof Cologne, said “It was exciting to realize that we could alter the structural organization of DNA simply by exerting mechanical forces on the stem cells.”
The force-sensing in the cells was tied to the protein emerin, which links the cell nucleus and DNA to the cytoskeleton, the force bearing structure of the cell. Emerin is mutated in Emery-Dreifus muscular dystrophy, which results in degeneration of mechanically strained skeletal muscle, heart, and skin tissue, according to the release.