Different types of resident adult stem cells exist in mammalian organs in order to maintain tissue homeostasis and organ repair. Even though the heart has low regenerative capacity it has been demonstrated that resident adult stem cells exist and are able to replace smooth muscle cells, endothelial cells and damaged or lost cardiomyocytes. Currently, the origin and the identity of cardiac resident adult stem cells remain controversial. In this study, descendants of cells that have expressed Sca1, which is one of the most widely used adult stem cell markers, were traced. Their contribution to self-renewal in the heart during aging and under pathological conditions was characterized. In both conditions, Sca1-expressing cells could differentiate into three major cardiac lineages, providing evidence of their role in myocardial renewal. These cells appeared to be a heterogeneous population in vivo as well as at a transcriptomic level, showing a specific location in the heart. Unlike the heart, skeletal muscle shows a high regenerative potential. It contains adult resident progenitor cells called satellite cells , which are able to differentiate into mature muscle fibers. Although satellite cells are considered to be the principal stem cells in the skeletal compartment, recent works have identified alternative sources of multipotent stem cells that are positive for Sca1. In this study, an in vivo lineage tracing approach in skeletal muscle revealed that Sca1-expressing cells are involved in skeletal muscle regeneration, although their contribution is lower compared to satellite cells. It was also possible to identify a small population of Sca1-expressing cells able to differentiate into muscle fibers without expressing Pax7, a marker for satellite cells known to be involved in quiescence, proliferation and differentiation of myogenic cells. Furthermore, the plasticity of satellite cells and Sca1-expressing cells was tested in vivo and was confirmed by gene expression profiling analysis. The data obtained verified that satellite cells are unipotent stem cells only able to regenerate skeletal muscle fibers. In contrast to satellite cells, Sca1-expressing cells are revealed to be multipotent and have the ability to differentiate into adipocytes and osteoblasts.In conclusion, this study confirmed the presence of Sca1-expressing cells that are able to contribute to myocyte regeneration in the heart and skeletal muscle. Further characterization of these Sca1-expressing cells will provide valuable insights into the molecular mechanisms regulating cardiac and muscle stem cells in humans. Importantly, this could aid the future development of therapeutic strategies for human cardiac and skeletal muscle diseases.
Verknüpfung zu Publikationen oder weiteren Datensätzen
