| In adult animals, muscle regeneration is thought to be mediated primarily by tissue specific-stem cells, known as satellite cells. Their definitive origin is debated. In adult GFP+ bone marrow transplant recipients, we demonstrate the existence of bone marrow-derived (BMD) myogenic satellite cells. BMD satellite cells do not arise through fusion with existing satellite cells, and are shown to have biochemical, anatomical, and behavioral characteristics identical to those of satellite cells in the context of muscle regeneration. BMD satellite cells fuse with nascent and mature myofibers during the course of muscle regeneration. They are recruited from a pool of hematopoietic stem cell-derived circulating cells, by damage-generated signals, into the muscle tissue where they await subsequent cues from their surrounding environment to participate in regeneration of damaged myofibers. Moreover, this transition from blood into muscle is not exclusively a transplantation related phenomenon, for as shown here it occurs under normal physiological conditions. BMD satellite cell activity appears to be governed by the same well-defined factors that also control the proliferation and differentiation of the canonical muscle stem cell, the satellite cell. Therefore, BMD satellite cells represent a previously unrecognized sub-population of myogenic satellite cells that functions in regeneration of skeletal muscle. |
