Skin cells' potential to form muscle cell models

A new research study has tested the ability of skin cells to form muscle in the lab. This will help researchers to decide what kinds of cells to use when investigating muscle conditions.
The use of cells in muscle research 

When scientists need to study how our muscle forms and grows, and to understand how this can go wrong, it’s useful for them to have cells that can be grown in a laboratory and stimulated to form muscle-like structures as cellular models. Different experiments can then be carried out on these cells to help us understand conditions that affect the muscle. 

However, obtaining muscle cells can be challenging, as it requires a muscle biopsy, which can be painful and uncomfortable for the person having it. An alternative is to use skin cells. It’s possible to take a tiny sample of a person’s skin, extract cells called fibroblasts, and re-programme them by placing a muscle gene in them so they form muscle-like structures. However, to date, it has been unclear whether these skin-derived cells are a close model to that of muscle, and whether a cell that has come from skin can be made to behave like a muscle cell. 

A new study of muscle cells developed from skin cells 

Researchers at the University of Oslo and the Centre for Muscle Research in Paris compared both skin and muscle derived cells in a study funded by Muscular Dystrophy UK and CureCMD. For the first time, they were able to compare both types of cells from the same person. This is important, because it means differences between the cells can’t be due to genetic differences between people. 

The researchers found that muscle-like tissue formed from the skin-derived cells was similar in some ways to that formed by muscle cells. During muscle formation, the skin-derived cells, which are called ‘Myo-converted Fibroblasts’, switched on the same genes as muscle cells. This means that, like muscle cells, they fused together to make larger elongated cells resembling the long fibres of which muscle in the body is composed. However, there were differences in the behaviour of the cells’ nuclei. Most cells have one nucleus – a structure that, in each cell, houses a complete copy of our DNA. When muscle cells fuse together to form myotubes, which are larger elongated cells like fibres, there is a period during which the nuclei of each myotube are arranged in a line. The nuclei in the skin-derived cells did not form these lines.  

The researchers also studied the structure of the DNA inside the cells – in particular which parts of the DNA were pinned to a mesh-like structure called the nuclear lamina that coats the inner surface of the nucleus. This association of DNA to the lamina is important because it can regulate how cells form into muscle – genes that are inside lamina-pinned DNA are usually switched off. The skin-derived cells had some similarities but also some important differences with muscle cells. For example, certain genes involved in the movement of cells were lamina-pinned only in muscle cells and not in the skin-derived cells. 

What this means for the future 

This work will be valuable in helping researchers to decide which cell models to use in the study of muscle conditions. It also raises interesting questions about how muscle formation is influenced by the architecture of our DNA within the nucleus, which we hope will be addressed in the future.  

 

For more information, see the original article here

This piece is written by Bill Duddy. Bill is a lecturer in the neuromuscular research team at Ulster University School of Medicine. He lost his brother to Duchenne muscular dystrophy, has devoted his career to the understanding and treatment of neuromuscular conditions, and enjoys explaining science.

 

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