The First Characterization of a Novel Stem Cell Population and the Temporal Relationship with Satellite Cells in Human Skeletal Muscle (2018)

Skeletal muscle possesses the remarkable ability to repair itself in response to a damaging stimulus. Muscle repair or myogenesis is driven by the activation and proliferation of muscle-resident stem cells known as satellite cells (SC) and the subsequent fusion or donation of myonuclei into skeletal muscle fibers. Although SC have been identified as the main skeletal muscle progenitor, several other unique cell populations have been recognized as contributing to skeletal muscle plasticity. PW1+ interstitial cells or PICs have been recently defined as a muscle-resident stem cell population that is anatomically and functionally distinct from Pax7+ expressing SC. This population has previously only been identified in murine and porcine models. PICs are derived from a different cell lineage than that of SC and are located in the interstitium outside of the SC niche. Yet, PW1+ expression has also been colocalized with Pax7+ expressing SC indicating a possible interaction or transitive property of SC to exhibit PW1 expression. Therefore the objective of this investigation was to identify PICs in human skeletal muscle tissue and to examine the temporal relationship and quantify the proliferation of both PICs and SC in response to a single bout of muscle damaging eccentric exercise. Ten young adults (25 ± 3yr; mean ± SEM) participated in a muscle damaging protocol involving eccentric loading of the quadriceps muscle on an isokinetic dynamometer. A total of 300 contractions, separated into 30 sets of 10 repetitions, was performed at 180°/s over a range of 60° of movement with one-minute of rest between consecutive sets. Percutaneous needle biopsies from the vastus lateralis were taken pre-damage and 6h, 24h, 72h, and 96h post eccentric damage. In response to single bout of eccentric exercise, total Pax7+ cells/100 myofibers remained unchanged at 6h (8.9 ± 1.8 cells/100 myofibers), 24h (9.1 ± 1.1 cells/100 myofibers), but significantly increased at 72h (11.2 ± 1.4 cells/100 myofibers) and 96h (10.2 ± 1.2 cells/100 myofibers) as compared to Pre (7.6 ± 1.0 cells/100 myofibers). PW1+ interstitial cells/100 myofibers remained unchanged at all timepoints following damage. However, total PW1+ cells/100 myofibers increased at 72h (3.1 ± 1.2 cells/100 myofibers) and 96h (4.5 ± 1.7/100 myofibers), with no change at 6h (0.9 ± 0.3 cells/100 myofibers) and 24h (2.4 ± 0.9 cells/100 myofibers) as compared to Pre (0.6 ± 0.2 cells/100 myofibers). The expression of Pax7+/PW1+ in myofibers remained unchanged at 6h (0.2 ± 0.1 cells/100 myofibers) and 24h (0.2 ± 0.1 cells/100 myofibers) and 96h (0.9 ± 0.3 cells/100 myofibers), but significantly changed at 72h (1.0 ± 0.3 cells/100 myofibers). There was also a trend in the percentage of total SC expressing PW1 at 72h (10.4 ± 3.2 % SC expressing PW1), p=0.082) when compared to Pre (4.1± 2.1% SC expressing PW1). Here, for the first time in human skeletal muscle, we identify a population of PW1+ interstitial cells that appear to be exercise-responsive. We also show that PW1 colocalizes with a subset of muscle SC. The exact contribution of PW1 to skeletal muscle repair/adaptation in humans is not fully understood, however this data supports the notion that atypical myogenic progenitors may contribute to physiological cues in humans. Support or Funding Information The Natural Sciences and Engineering Research Council of Canada (NSERC) Representative image of a DAPI/Laminin/Pax7/PW1 stain of a muscle cross section. *; represents SC, arrow represents PIC This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.