SATELLITE CELL-PROLIFERATION AND THE EXPRESSION OF MYOGENIN AND DESMIN IN REGENERATING SKELETAL-MUSCLE - EVIDENCE FOR 2 DIFFERENT POPULATIONS OF SATELLITE CELLS

BACKGROUND: Regeneration of mature skeletal muscle recapitulates close ly fetal myogenesis. It is initiated by activation of the reserve myog enic precursor cells, the satellite cells, which proliferate, differen tiate into myoblasts expressing muscle-specific proteins, fuse into my otubes, and finally mature into myofibers. The MyoD family of transcri ption factors participates in the regulation of the complex phenomenon of myogenic differentiation during development and in vitro. The func tion of these transcription factors in the regeneration of injured mat ure skeletal muscle in vivo is, however, still unclear. EXPERIMENTAL D ESIGN: To clarify the primary events in myogenic precursor cell activa tion, the expression of myogenin was examined in rats 1 to 48 hours af ter either a contusion injury to the gastrocnemius or after toxic inju ry to the soleus muscle. Myogenin mRNA expression was studied by North ern blot hybridizations, and the results were correlated with the onse ts of the mitotic activity (i.e., incorporation of bromodeoxyuridine) of the satellite cells and of the production of the myogenin and MyoD1 proteins, as well as muscle-specific intermediate filament protein, d esmin. RESULTS: Both forms of muscle injury produced myofiber necrosis , followed by the activation of the satellite cells. The first sign of myogenic differentiation, an increase in myogenin mRNA expression, oc curred between 4 and 8 hours after injury. The first desmin-, MyoD1- a nd myogenin-positive myoblasts were seen after 12 hours, but satellite cell proliferation was not seen until 24 hours after the injury. CONC LUSIONS: The schedule of the events in our study contradicts the gener al concept that differentiation should follow proliferation. To explai n this discrepancy, we propose that there are two populations of precu rsor cells: committed satellite cells, which are ready for immediate d ifferentiation without preceding cell division, and stem satellite cel ls, which undergo mitosis before providing one daughter cell for diffe rentiation and another for future proliferation.