Bmi1 Is Expressed in Postnatal Myogenic Satellite Cells, Controls Their Maintenance and Plays an Essential Role in Repeated Muscle Regeneration

Abstract

Satellite cells are the resident stem cell population of the adult mammalian skeletal muscle and they play a crucial role in its homeostasis and in its regenerative capacity after injury. We show here that the Polycomb group (PcG) gene Bmi1 is expressed in both the Pax7 positive (+)/Myf5 negative (−) stem cell population as well as the Pax7+/Myf5+ committed myogenic progenitor population. Depletion of Pax7+/Myf5− satellite cells with reciprocal increase in Pax7+/Myf5+ as well as MyoD positive (+) cells is seen in Bmi1−/− mice leading to reduced postnatal muscle fiber size and impaired regeneration upon injury. Bmi1−/− satellite cells have a reduced proliferative capacity and fail to re-enter the cell cycle when stimulated by high serum conditions in vitro, in keeping with a cell intrinsic defect. Thus, both the in vivo and in vitro results suggest that Bmi1 plays a crucial role in the maintenance of the stem cell pool in postnatal skeletal muscle and is essential for efficient muscle regeneration after injury especially after repeated muscle injury.

Modeling Clear Cell Sarcomagenesis in the Mouse: Cell of Origin Differentiation State Impacts Tumor Characteristics

“…Since it has previously been demonstrated that Bmi1 is expressed in Pax7-positive satellite cells within muscle (Robson et al, 2011), it is possible that the intramuscular Bmi1 -lineage tumors could arise from this cell population. However, we already discussed that Pax7 CreERT2 ; Rosa26 EA1 do not form tumors, arguing against the possibility that satellite cells provide a potential cell of origin for CCS (Figure S2D and E).…”

Cyclin D3 critically regulates the balance between self-renewal and differentiation in skeletal muscle stem cells

“…Notably, the defects of cyclin D3-null satellite cells are similar to those displayed by satellite cells with disrupted function of the Polycomb proteins Ezh2 or Bmi1 51,59. Indeed, Polycomb complexes are known to play a pivotal role in maintaining the self-renewal capability of various adult stem cells by binding directly and repressing the promoter of p16, a specific inhibitor of the activity of cyclin D-dependent kinases 60–64.…”

Proteomic and Functional Analyses Reveal the Role of Chromatin Reader SFMBT1 in Regulating Epigenetic Silencing and the Myogenic Gene Program*

“…4B). On the other hand, expression of the muscle stem cell factors Bmi1 (26) and Nestin (27) was decreased when Sfmbt1 was depleted, suggesting a role of Sfmbt1 in the maintenance of the muscle stem cell state. Our findings thus support that Sfmbt1 criti- .…”