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Ebb and Flow

Posted on March 28, 2019

Muscle stem cells are mighty. They have to be – they have to act fast and be ready to repair muscle tissue at any time. Think about it: If you’re hurt during a sports activity or accident, or even if you lift weights and work out, your muscle stem cells have to be ready to regenerate new tissue as quickly as possible. But, how do muscles stem cells know when to stop regenerating?

Researchers from the Max Delbrück Center for Molecular Medicine have the answer.

It’s oscillation.

Oscillation, thought previously only to occur in brain stem cells, is the body’s mechanism to stop the uncontrolled differentiation of stem cells to prevent depletion.

The research team published their findings in the journal Genes and Development, reporting that two proteins, MyoD and Hes1, help to regulate how muscle stem cells differentiate. They also found that these proteins are produced in the stem cells in an oscillatory manner, in which production fluctuates depending on need.

The researchers were astonished at their findings, as no one had previously found that these proteins in muscle tissue oscillated.

The study authors hope that one day their research will lead to better treatments of muscle disorders, such as muscular dystrophies, acute myopathy, myositis and sarcopenia, a syndrome characterized by the progressive loss of muscle mass as a result of the aging process.

The study also revealed that the production of muscle cells runs entirely every two to three hours.

During their research, the scientists connected the Hes1 and MyoD proteins to light-emitting proteins to monitor and track their development and behavior.

The researchers then observed that in specific muscle cells in living animals, the Hes1 protein was created in an ebb-and-flow, oscillating manner.

The researchers found that every two to three hours, the Hes1 reached its peak production. The same thing happened with the MyoD protein. As long as the quantity of the protein fluctuated periodically, the muscle stem cells stopped growing and dividing and creating muscle tissue.

This regeneration also ensures that there is always a backup supply of muscle stem cells ready.

The study authors also tested their theory by turning off the gene that controls the production of Hes1. They found that once Hes1 was completely turned off, it led to MyoD production also stopping in an oscillatory manner. MyoD was then produced in a stable pattern, and stem cells began to regenerate themselves.

The next step for the researchers is to study why oscillation of MyoD inhibits stem cell differentiation and why stable production of the protein is required to make new cells.

“Understanding how these cells work could mean a world of difference for those living with muscle diseases,” said Dr. Joel Singer, a New York personal cell physician.

One of the most well-known muscle conditions is muscular dystrophy, an umbrella term for several rare genetic diseases that cause progressive weakness and loss of muscle mass.

Muscle conditions affect both men and women, but the majority of those affected are male.

“These conditions have no cure, and treatments are typically designed to slow down the progression of the disease,” Singer said.

In most cases, abnormal genes cause muscle degeneration, and most symptoms begin to show in childhood. Over time, damaged muscles get weaker, and affected individuals see changes in their ability to move. Advanced cases can impact breathing, swallowing and digestion.

Source: Max Delbrück Center for Molecular Medicine in the Helmholtz Association. “Oscillation in muscle tissue.” ScienceDaily. ScienceDaily, 15 March 2019.

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