Figure 3. Non-random segregation of chromosomes and asymmetric fate determination.

The satellite cell pool is composed of primitive (Pax7hi, green) and lineage primed (Pax7low, grey) subsets. Pax7hi cells are in a dormant (less metabolically active) state. Pax7low satellite cells are lineage-primed. Following cytokinesis, satellite cell daughters can each inherit some chromosomes bearing newer (purple) or older template strand (dark green). Pax7hi subsets undergo non-random segregation of chromosomes, whereby one daughter contains exclusively chromosomes bearing older template strands, while its sister contains only chromosomes bearing newer template strands. In contrast, Pax7low cells undergo random segregation of chromosomes ensuring each daughter cell inherits an older and newer template strand. Subsets of Pax7hi and Pax7low are capable of multiple rounds of self-renewal (curved arrows) and differentiation (blue cells), however Pax7hi cells are endowed with enhanced self-renewal capability. Daughter cells containing newer template strands express high levels of Numb, Myod and Dek1 and are biased to differentiate (blue cell). Pax7hi cells can give rise to Pax7low, but not vice versa, suggesting a hierarchical relationship in the satellite cell pool based on Pax7 expression. In addition to cell fate determination, non-random segregation of chromosomes may act to protect genome integrity during cell proliferation. Due to low metabolic output of primitive satellite cells they may be protected from oxidative damage. Lineage-primed satellite cells are capable of self-renewal but may be acutely sensitive to proliferative demands and other forms of genotoxic insults.