Transcriptome analysis and microRNAs profile of mesodermal iPSCs derived progenitors

Mesodermal iPSC derived progenitors (MiPs) obtained from human fetal fibroblasts and skeletal muscle mesoangioblasts show a different myogenic potential in vitro and when injected in vivo in mice model of Muscular Dystrophy. MAB-MiPs hold greater myogenic commitment compared to f-MiPs, showed by increased engraftment and regeneration of the hindlimb muscle. Here we report that RNA sequencing of MiPs and of induced pluripotent stem cells (iPSCs) of origin allows identification of genes differentially regulated between fibroblast and MABs progenies that might be responsible for the different contribution to muscle regeneration. MicroRNA- sequencing of the same cell lines further allowed a selection of a set of miRNAs that can drive the myogenic propensity of MiPs in vivo and identification of promyogenic and antimyogenic miRNA cocktails. Manipulation of the selected miRNAs improved the engraftment and regeneration of MiPs. Additional RNA-sequencing after the treatment with the defined promyogenic and antimyogenic cocktails unraveled additional information on the pathways modulated by the selected factors. mRNA and microRNA profile of n=3 f-MiPs, f-iPSCs, MAB-MiPs, MAB-iPSCs and additional mRNA profile of n=3 f-MiPs and MAB-MiPs before and after treatment with antimyogenic and promyogenic cocktails.