After injury, even adult muscles can heal very well because they have a reserve supply of muscle stem cells, called satellite cells, which they can utilize for repair. Until now, it was unclear how this supply of satellite and muscle progenitor cells, out of which both muscle cells as well as satellite cells develop, keeps itself “fresh”. Developmental biologists Professor Carmen Birchmeier, Dr. Elena Vasyutina, and Diana Lenhard of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now demonstrated that a molecular switch, abbreviated RBP-J, regulates this “fountain of youth”. If the switch is absent, the satellite cells generate muscle cells in an uncontrolled way, resulting in the depletion of the satellite cell reserves. As a consequence, too few muscles form during the developmental phase of a living organism and the fetus can no longer build up a reserve supply of satellite cells. The MDC scientists’ research report, which could be of significance for the future development of stem cell therapies, has just been published in the online edition of the Proceedings of the National Academy of Sciences (PNAS)*.
(Photo: Dr. Elena Vasyutina/Copyright: MDC)
Muscle stem cells were discovered in the beginning of the 1960s. For a long time, researchers could only identify them with the aid of an electron microscope. These cells are located between the muscle cell membrane and the layer surrounding it (the basal membrane). It has been known for some time that satellite cells have characteristic surface molecules and transcription factors which allow researchers to find these cells more easily.
The RBP-J switch is involved in a signaling pathway which is critical for cell communication, the Notch signaling pathway, and is known to be a key mediator of signaling information. The signaling pathway plays a major role both in the development of a living organism and in the adult organism.
The researchers’ evidence that satellite cells and muscle progenitor cells preserve their stem cell character because RBP-J makes them persist in an earlier developmental stage takes on special significance against the background of previous stem cell therapy experiments. Other research groups have previously shown that muscles regenerate very well when satellite cells are directly injected into the muscles of mice. Moreover, due to this, the muscles also replenish their reserves of satellite cells. Influencing RBP-J could improve therapies that are based on satellite cells.
*RBP-J (Rbpsuh) is essential to maintain muscle progenitor cells and to generate satellite cells
Elena Vasyutina1*, Diana C. Lenhard1*, Hagen Wende1, Bettina Erdmann1, Jonathan A. Epstein2, and Carmen Birchmeier1#
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany 2 Department of Cell and Developmental Biology and the Cardiovascular Institute, University of Pennsylvania, 954 BRB II, 421 Curie Boulevard, Philadelphia, PA 19104, USA
*These authors contributed equally to the work
#Corresponding author: Carmen Birchmeier