iNs, as both cell types appeared to show cell-type-specific, age-dependent expression profiles (Figure 4D; Table S3). GO term and KEGG pathway analysis revealed that, in fibroblasts, genes involved in wound healing, stress response, and Ca2+ signaling—which are categories that have been previously been implicated in skin aging—were significantly altered (Figure 4E; Table S6) (Adler et al., 2007; Fraser et al., 2005; Lu et al., 2004; Murphy, 2006; Peterson et al., 1985; Rando and Chang, 2012). Enriched gene categories in aging iNs related to functional neuronal categories such as Ca2+ homeostasis, neuron projection, and regulation of synaptic plasticity (Figure 4F). Most interestingly, several genes from these categories, namely calcitonin (Calca), the cation channel Trpc6, the endothelin receptor Ednrb, and the catenin Ctnna1 also relate to the GO term “aging” (GO:0007568), which was also enriched in our aging iN system (Table S6).
