Contribution of Retinoid X Receptor Signaling to the Specification of Skeletal Muscle Lineage

dc.contributor.authorQiao, Li
dc.contributor.authorLeMay, Melanie
dc.contributor.authorMach, Hymn
dc.contributor.authorLacroix, Natascha
dc.contributor.authorHou, Chenchen
dc.contributor.authorChen, Jihong
dc.description.abstractPluripotent stem cells possess a tremendous potential for the treatment of many diseases because of their capacity to differentiate into a variety of cell lineages. However, they provide little promise for muscle-related diseases, mainly because of the lack of small molecule inducers to efficiently direct myogenic conversion. Retinoic acid, acting through the retinoic acid receptor (RAR) and retinoid X receptor (RXR), affects stem cell fate determination in a concentration-dependent manner, but it only has a modest efficacy on the commitment of ES cells into skeletal muscle lineage. The RXR is very important for embryonic development but is generally considered to act as a silent partner of RAR in a non-permissive mode. In this study, we have examined whether activation of the RXR by rexinoid or RXRspecific signaling play a role in the specification of stem cells into muscle lineage. Our findings demonstrate that mouse ES cells generate skeletal myocytes effectively upon treatment with rexinoid at the early stage of differentiation and that on a molecular level, rexinoid-enhanced myogenesis simulates the sequential events observed in vivo. Moreover, RXR-mediated myogenic conversion requires the function of -catenin but not RAR. Our studies establish the feasibility of applying the RXR agonist in cell-based therapies to treat muscle-related diseases. The aptitude of mouse ES cells to generate skeletal myocytes following rexinoid induction also provides a model system to study the convergence of different signaling pathways in myogenesis.
dc.description.sponsorshipThis work was supported by an operating grant from the Natural Sciences and Engineering Research Council of Canada and by a graduate scholarship award from the Canadian Institutes of Health Research (to M. L.); and by a grant from the University of Ottawa Author Fund in support of Open Access Publishing
dc.subjectPluripotent stem cells
dc.subjectRetinoic acid receptor
dc.subjectRetinoid X receptor
dc.subjectMuscle lineage
dc.subjectSkeletal muscle development
dc.titleContribution of Retinoid X Receptor Signaling to the Specification of Skeletal Muscle Lineage
CollectionPathologie et médecine de laboratoire // Pathology and Laboratory Medicine
Publications en libre accès financées par uOttawa // uOttawa financed open access publications