Fig. 6

Targeted genome-wide application of CRISPR-Cas9 replicates transdifferentiation dynamics. a Chromosomal distribution of genes that contain a region of partial homology. Genes in the inner circle (green) do not have a flanking PAM sequence, while those in the outer circle (CRISPR target genes) do. Y-axis corresponds to the length of homologous seed region. b GO enrichment analysis (top) of the genes with a consensus CRISPR recognition motif (bottom sequence logo) revealed their involvement in cell-matrix interaction and regulation of cytoskeleton. c The top plots show expression of selected genes 12 h after application of TDi-RNA (Nuc: Cas9 nuclease, Nic: Cas9 Nickase). The middle plots show expression of the same genes 2 (D2) and 7 days (D7) after neural induction in control pericytes. The bottom plots show expression of selected genes 12 h after application of TDi-RNA (Cas9 nuclease) and in incubation a serum-free medium. Magenta: downregulation with p < 0.05, turquoise: upregulation with p < 0.05, grey: non-significant. d Panel shows immunohistochemical identification of three selected proteins before (Ct.) and after application of TDi-RNA and incubation of programmed cells in growth medium (GM) or in serum-starved condition (SS). A model is proposed whereby autophagy and double-stranded DNA breaks (DDBs) act synergistically to propel de-differentiation and subsequent neural differentiation during the transdifferentiation of pericytes