RNA-seq and ChIP-seq profiling of human iPSCs, derived NSCs and human fetal NSCs (ChIP-Seq)
Human iPSC-derived neural stem/progenitor cells (hiPSC-NSCs) are a promising source for cell/gene therapy approaches to target neurodegenerative and demyelinating disorders with unmet clinical needs. Despite the great effort in characterizing hiPSC-derived products in both in vitro and in vivo settings, we still lack a comprehensive study addressing hiPSC-NSC identity and safety at genome-wide level, an issue of paramount importance to establish accepted criteria for prospective clinical applications. Here, we evaluated the transcriptional (by poly-A+ RNA-seq) and epigenetic (by H3K27Ac ChIP-seq) signatures in hiPSCs and differentiated hiPSC-NSC progeny, keeping as reference a somatic clinically relevant human fetal NSC (hfNSCs) line. Overall, our comprehensive transcriptomic and epigenomic analysis coupled to a long-term functional in vivo characterization provided insight into the cell identity, safety profile, and therapeutic potential of hiPSC-NSCs, supporting the rationale for the continuous development of hiPSC-NSCs as an alternative source to somatic hfNSCs for treatment of neurodegenerative and demyelinating disorders. Overall design: We performed the poly-A+ RNA-seq and ChIP-seq (for H3K27 Acetilation) profiling of three replicates of a human fetal neural stem cell (hfNSC) cell line, four replicates of human induced pluripotent stem cells (hiPSCs) obtained by reprogramming of healthy skin fibroblasts (two from adult fibroblasts and two from newborn fibroblasts), and four replicates of neural stem cells (NSCs) differentiated from hiPSCs (two from the adult hiPSCs and two from the newborn hiPSCs).