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Global transcriptional characterization of differentiating non-human primate (cynomolgus) iPAX7 iPS cells and comparison with their human counterpart

ABSTRACT: Pluripotent stem (PS) cells enable the scalable production of tissue-specific derivatives with therapeutic potential for various clinical applications, including muscular dystrophies. Given the similarity to human counterparts, the non-human primate (NHP) is an ideal preclinical model to evaluate several questions, including delivery, biodistribution and immune response. While the generation of human induced PS (iPS) cell-derived myogenic progenitors is well established, there has been no data for NHP counterparts, probably due to the lack of an efficient system to differentiate NHP iPS cells towards the skeletal muscle lineage. Here we report the generation of three independent Macaca fascicularis iPS cell lines and their myogenic differentiation using PAX7 conditional expression. Whole transcriptome analysis confirmed the successful sequential induction of mesoderm, paraxial mesoderm, and myogenic lineages. NHP myogenic progenitors efficiently gave rise to myotubes under appropriate in vitro differentiation conditions and engrafted in vivo into TA muscles of NSG and FKRP-NSG mice. Lastly, we explored the pre-clinical potential of these NHP myogenic progenitors in a single wild-type NHP recipient, demonstrating engraftment and characterizing the interaction with the host immune response. These studies establish an NHP model system in which to study iPS cell-derived myogenic progenitors.

ORGANISM(S): Macaca fascicularis Homo sapiens

PROVIDER: GSE228567 | GEO | 2023/05/03

REPOSITORIES: GEO

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