To test if potentially concealed transcriptomic aging signatures reappeared following neuronal differentiation of iPSCs, we directly converted iPSCs from a subset of donors into neurons using the same N2A-based approach, PSA-NCAM-based FACS purification, and RNA-seq (Figure S7). As expected, iPSC-iNs showed very little significant transcriptomic aging signs. Differential expression analysis showed a 19-fold lower number of age-dependent genes in iPSC-iNs than in the corresponding fibroblast-derived iNs from the exact same subset of donors (12 versus 227 genes, respectively; Figure S7). None of these genes overlapped with any of the fibroblasts or iN aging genes and only one gene overlapped with the cortex aging genes. These data suggest that, following differentiation, iPSC derivatives, at least the iNs, remain in a largely rejuvenated state.
