Source online “Native collagen VI delays muscle stem cell early differentiation” – Samuele Metti et al. J Cell Sci. 2024 –

Muscle stem cells are normally found in the muscle and are quickly activated after damage to regenerate tissue, replacing damaged muscle fibers and allowing for the full recovery of the entire muscle’s contractile functionality. Muscle stem cells reside in a particular environment called the ‘niche,’ which consists of multiple actors: the muscle fiber, blood capillaries, certain immune system cells, and, most importantly, a unique combination of ‘extracellular matrix’ proteins, which are secreted outside the cells and regulate many aspects of the niche, consequently influencing the behavior of the stem cell.

A key component of the extracellular matrix of the stem cell niche is Collagen VI, a protein belonging to the collagen family and with very peculiar, not to say unique, chemical characteristics. The role of Collagen VI in skeletal muscle, particularly in the regulation of muscle stem cells, is a continually active research area in the laboratory of Prof. Paolo Bonaldo at the University of Padua.

In past scientific publications, Prof. Bonaldo’s research group focused mainly on the ability of Collagen VI to regulate the mechanical, or rather bio-mechanical, properties of the stem cell niche. Indeed, in the famous Col6 knock out mice generated by Prof. Bonaldo, a decrease in the rigidity of the niche is observed in the absence of Collagen VI in the extracellular matrix. This decreased rigidity of the niche alters the behavior of the stem cells which, becoming overly active, contribute to the onset of myopathy.

In this new article, instead, signed by Samuele Metti and Francesco Da Ros, a new role of Collagen VI in regulating the functionality of muscle stem cells is highlighted for the first time. Samuele and Francesco realized that Collagen VI also acts as a chemical (or biochemical) signal, independently of regulating the rigidity of the niche. In fact, when Collagen VI is provided to muscle stem cells cultured in the laboratory, it slows their proliferation, making them less active and preserving their stem cell potential.

This new discovery brings us closer to understanding all the functions that Collagen VI performs within skeletal muscle, and at the same time raises other important biological questions that Prof. Bonaldo’s laboratory and other laboratories around the world will try to answer in the coming years.”