| Abstract: |
Satellite cells are muscle stem cells that have important roles in postnatal muscle growth and adult muscle regeneration. Although fastand slow-dividing populations in activated satellite cells have been observed, the functional differences between them remain unclear. Here we elucidated the relationship between proliferation behaviour and satellite cell function. To assess the frequency of cell division, satellite cells isolated from mouse EDL muscle were labelled with the fluorescent dye PKH26, stimulated to proliferate and then sorted by FACS. The vast majority of activated satellite cells were PKH26 low fast-dividing cells, whereas PKH26 high slow-dividing cells were observed as a minority population. The fast-dividing cells generated a higher number of differentiated and self-renewed cells compared with the slow-dividing cells. However, cells derived from the slow-dividing population formed secondary myogenic colonies when passaged, whereas those from the fast-dividing population rapidly underwent myogenic differentiation without producing self-renewing cells after a few rounds of cell division. Furthermore, slow-dividing cells transplanted into injured muscle extensively contributed to muscle regeneration in vivo. Id1, a HLH protein, was expressed by all activated satellite cells, but the expression level varied within the slow-dividing cell population. We show that the slow-dividing cells retaining long-term self-renewal ability are restricted to an undifferentiated population that express high levels of Id1 protein (PKH26 highId1 high population). Finally, genome-wide gene expression analysis described the molecular characteristics of the PKH26 highId1 high population. Taken together, our results indicate that undifferentiated slow-dividing satellite cells retain stemness for generating progeny capable of long-term self-renewal, and so might be essential for muscle homeostasis throughout life. © 2012. |
| Keywords: |
controlled study; protein expression; nonhuman; flow cytometry; cell proliferation; animal cell; mouse; animals; mice; animal tissue; cells, cultured; cell division; cell function; gene expression profiling; inhibitor of differentiation 1; molecular dynamics; fluorescent dyes; animal experiment; cell renewal; in vivo study; cell differentiation; mice, scid; mice, inbred c57bl; mice, transgenic; stem cell; regeneration; cell subpopulation; cell count; mice, inbred nod; self-renewal; skeletal muscle; myoblasts; muscle regeneration; muscle development; skeletal muscle satellite cell; colony formation; satellite cells; fluorescence activated cell sorter; slow-dividing cells; stemness; muscle fibers, skeletal; satellite cells, skeletal muscle
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