Objectif
Stem cells are present in many adult tissues in a quiescent state. Their contribution to tissue repair depends on their activation, leading to proliferation and subsequent differentiation or return to quiescence. Skeletal muscle provides a model in which to study adult stem cell behavior. This tissue regenerates after injury and the muscle satellite cell is key to this process. These quiescent cells, located under the basal lamina of muscle fibres become activated upon injury, proliferate and differentiate into new muscle fibres or revert to quiescence. Examining the different states that a satellite cell can adopt under physiological conditions should lead to the identification of new regulators of myogenesis, and contribute to a better understanding of the mechanisms controlling quiescence and activation. Transcriptome analysis were performed on purified satellite cells isolated from adult muscles where these cells are quiescent and from growing or regenerating muscles, where they are activated. This analysis provided new insights into the genes differentially expressed in both states. My project will be to follow up on this work by focusing on three genes, Dach1, Meox2 and Pitx2/3. Those genes encode transcription factors whose profiles suggest they are involved in the function of muscle adult stem cells. Proliferation and differentiation of satellite cells will be studied in vivo in regenerating muscles of Pitx2/3 conditional mutant mice, or after inhibition of Dach1 and Meox2 expression by RNAi viral infection of injured muscle. Similarly, ex vivo proliferation and differentiation of satellite cells in single fibers and primary cultures will be analyzed after Dach1 or Meox2 knock-down by RNAi. Conversely, the consequences of the over-expression of these genes will be investigated in single fiber preparations and cultured satellite cells. These experiments are expected to give insights into the role of these genes in the physiology of satellite cells.
Champ scientifique
Appel à propositions
FP7-PEOPLE-2009-RG
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Régime de financement
MC-IRG - International Re-integration Grants (IRG)Coordinateur
75724 Paris
France