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Gene expression profiling of CHIR99021-induced skeletal myogenesis in human pluripotent stem cells

ABSTRACT: Human pluripotent stem cell- (hPSC)-derived skeletal muscle progenitors (SMP)—defined as PAX7-expressing cells with myogenic potential—can provide an abundant source of donor material for muscle stem cell therapy owing to the near-infinite replication potential of PSCs. As in vitro myogenesis is decoupled from in vivo timing and the 3D-embryo structure, it remains difficult to definitively characterize what stage or type of muscle is modeled in culture. Here, gene expression profiling is analyzed in hPSCs over a 50 day skeletal myogenesis protocol and compared to gene expression datasets of other hPSC-derived skeletal muscle and adult murine satellite cells. Furthermore, day 2 cultures differentiated with high or lower concentrations of CHIR99021 were contrasted. Expression profiling of the 50 day time course identified successively expressed gene subsets involved in mesoderm/paraxial mesoderm induction, somitogenesis, and skeletal muscle commitment/formation which could be regulative by a putative cascade of transcription factors. Initiating differentiation with higher CHIR99021 concentrations resulted in significantly higher expression of MSGN1 and TGFB-superfamily genes, notably NODAL, resulting in enhanced paraxial mesoderm and reduced ectoderm/neuronal gene expression. Comparison to adult satellite cells revealed that genes expressed in day 50 cultures correlated better with those expressed by quiescent or early activated satellite cells, which have a greater therapeutic potential than late activated satellite cells. Day 50 cultures were similar to other hPSC-derived skeletal muscle and both expressed known and novel SMP surface proteins.

ORGANISM(S): Homo sapiens

PROVIDER: GSE131125 | GEO | 2019/09/13

REPOSITORIES: GEO

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