Lineage Decision From Pluripotent Stem Cells
The Perlingeiro laboratory was the pioneer in succeeding to generate skeletal muscle progenitors from embryonic stem (ES) cells. Their approach focuses on the use of master regulators of embryonic myogenesis to recapitulate muscle development in the Petri dish, generating myogenic progenitor cells with the capacity to restore muscle function following their engraftment in dystrophic mice. The recent breakthrough of direct reprogramming adult mouse and human fibroblasts toward a pluripotent state has opened new opportunities for the generation of patient- and disease- specific stem cells without the ethical issues associated with the derivation of human embryonic stem (ES) cells. These researchers have recently succeeded in applying their technology to mouse and human skin reprogrammed cells to generate large numbers of skeletal muscle progenitors as observed with their embryonic counterparts. When transplanted in mouse models of muscular dystrophy, these pluripotent cell-derived skeletal myogenic progenitors are capable of significant regeneration. Importantly, engrafted muscles are clearly endowed with superior specific force when compared to non-treated controls. Thus studies from this lab provide proof-of-principle for the future application of iPS cells. They are also interested in dissecting the role of TGF-beta signaling in mesoderm specification and commitment to the hematopoietic, endothelial, and cardiac lineages. They use MSI resources for bioinformatic analyses of our RNA-seq and ChIP-Seq studies.
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