Controlled differentiation of myoblast cells into fast and slow muscle fibers.

Skeletal muscles are classified into fast and slow muscles, which are characterized by the expression of fast-type myosin heavy chains (fMyHCs) or slow-type myosin heavy chains (sMyHCs), respectively. However, the mechanism of subtype determination during muscle fiber regeneration is unclear. We have analyzed whether the type of muscle is determined in the myoblast cells or is controlled by the environment in which the muscle fibers are formed from myoblast cells. When myoblast cells from 7-day-old chick embryo were cultured and formed into muscle fibers, more than half of the fibers produced only fMyHCs, and the remaining fibers produced both fMyHCs and sMyHCs. However, when myoblast cells were cultured in medium supplemented with a small amount of slow muscle extract, the expression of sMyHCs in muscle fibers increased, whereas the expression of fMyHCs increased in the group supplemented with fast muscle extract compared with the control group. The same results were obtained when cloned mouse myoblast cells (C2C12 cells) were cultured and formed into muscle fibers. The data presented here thus show that the subtype differentiation of muscle fiber is controlled by the environment in which the muscle fiber forms.