Stem cell biologists at the Carnegie Institution and John Hopkins University, Maryland, US, have reported findings that could affect research into new therapies for inherited muscle disorders. Reporting in the journal Nature, a team led by Christoph Lepper suggests that distinct sets of genes regulate mammalian stem cell fate in adults versus embryos.
'We are just beginning to learn the basics of stem cell biology, and there are many surprises', says Allan Spradling, director of Carnegie's Department of Embryology, where the work took place.
Previous research from the same group, also published in Nature, gave evidence for the role of two genes, Pax3 and Pax7, in the development of mouse skeletal muscle cells from muscle stem cells. Both genes were shown to be active and essential in mouse embryonic muscle stem cells. This time around, Lepper silenced Pax3 and Pax7 in adult muscle stem cells (satellite cells) using a simple genetic trick, such that they are no longer active. As Lepper reported to the press: 'I was totally surprised to find that the muscle stem cells are normal without them'.
Intrigued, the researchers looked to see if the 'mutant' satellite cells behaved like their normal counterparts - namely, could they develop into muscle cells. Researchers injured leg muscles with a chemical and measured the extent to which muscle tissue was replenished. Remarkably, the mutant satellite cells were not compromised in their ability to differentiate into muscle cells, and could also replenished the pool of stem cells. By silencing Pax3 and Pax7 at intervals after birth, they concluded that the two are only important in stem cells for three weeks, whereupon they become redundant.
Adult stem cells are only activated upon injury, when muscle cells need replacing. Conversely, embryonic muscle cells give rise to their progenitors during embryogenesis. Different stimuli plausibly stimulate different sets of genes at these different ages. The genes that are important in adult stem cells are yet to be described. However the upshot is that age should be a consideration in the future development of stem cell therapies for inherited muscle disorders.