RanBP17 plays an upstream role for the cellular aging phenotypes (Figure 7E). Next, since iPSCs from old donors appeared to rejuvenate their transcriptome and restored RanBP17 expression (Figure 7F), we wondered whether iPSC reprogramming might reconstitute proper NCC in old donor-derived cells. To assess NCC in iPSCs that normally grow in dense colonies, we transferred 11 reporter iPSC lines to the PluriPro monolayer culture system and measured NCC (Figure 7G). As anticipated, we found that GFPnuc/RFPnuc ratios from young, middle-aged, and old donors were indeed very similar with regard to compartmentalization and no detectable age-dependent impairment was detectable (Figures 7H and 7I). These data indi cate that loss of RanBP17 is sufficient to impair NCC, and that iPSC reprogramming functionally restores NCC in old-derived cells.
