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Protection of the muscle stem cell state from premature differentiation

Student thesis: Doctoral Thesis

The extraordinary capacity of regeneration exists in just certain species and tissue types. Invertebrates, the cells that regenerate tissues are called stem cells.
During adulthood, damaged muscle tissue regenerates through Satellite stem cells that re-enter the cell cycle from a quiescent state, giving rise to new muscle tissue. During development, newly forming organisms build tissues through proliferating stem cells that renew the stem cell pool whilst generating myogenic stem cells which will eventually differentiate into muscle cells. For many years the Myogenic Regulatory Factors (Mrf) genes have been considered to be the main genes driving this proliferation in adult and fetal stages.
Mrf genes have been shown to be capable of inducing non-myogenic cells to enter the myogenic lineage in vitro, but their role and capabilities in vivo have been less well characterised.
Here we show, using the developing chicken model, that Mrf genes and related genes are not capable of prematurely upregulating terminal muscle differentiation before HH20. MyoD and other combinations of gene misexpression were however shown to be capable of inducing Myosin upregulation between HH20 and HH24 indicating the existence of a time-frame dependent protection of premature development. These results indicate that the Mrf genes have a reduced proficiency for inducing differentiation in vivo compared with in vitro likely due to the presence of currently unidentified additional factors.
Our results demonstrate that the current understanding of the signals and cues of muscle stem cell differentiation are still insufficient to exploit the regenerative capabilities of muscle tissues towards regenerative therapies. The possible additional factors required for muscle stem cell differentiation are also discussed.
Original languageEnglish
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Award dateMay 2016
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