New research by scientists at the University of Sheffield, published in Nature Communications, has identified a novel mechanism by which stem cells in skeletal muscles maintain a pool of stem cells to ensure long-term regenerative capacity.
The research team, led by Dr Anne-Gaëlle Borycki from the Department of Biomedical Science and in association with King’s College, London and the University of Strasbourg, reports that populations of stem cells that reside in skeletal muscles actively modify their immediate environment to support the maintenance of a pool of stem cells for future use.
This discovery helps us to understand how niches dynamically remodel to maintain lifelong capacity to repair tissues and organs, opening new avenues into understanding the cause of the decline in regenerative capacity of stem cells in aging skeletal muscles. It also provides a novel framework for future studies in the generation of biomaterials to enhance stem cell function for regenerative medicine.
Stem cells are known to operate within specialised environments (niches) which are made up of other types of cells that support the activity of stem cells, mainly through the release of growth factors and signalling molecules that stimulate the spread and self-renewal of stem cells.
However, little is known about the component of niches called the extra-cellular matrix, a network of proteins that are organised into ultrastructures such as the basal lamina that covers skeletal muscle fibres.
The team set out to investigate the composition of the basal lamina in the niche of skeletal muscle stem cells. They discovered that the composition changed upon injury or in the degeneration of muscles. Namely, Laminins alpha1 and alpha5, two proteins normally associated with the embryonic development of skeletal muscles, were re-expressed and deposited in the niche.
Using genetic studies, the researchers demonstrated that inactivating mutations in the gene coding for Laminin alpha1 impaired the self-renewing capacity of skeletal muscle stem cells and abolished the long-term regenerative capability of skeletal muscles.