Fig. 5: Transcriptional activation of neural and eye development master factors governs ciRPE reprogramming.
From: Chemical reprogramming of fibroblasts into retinal pigment epithelium cells for vision restoration
a Volcano plots illustrating TFs with differences in regulon activity across various cell types during reprogramming from SCENIC. b The bar-dash plot shows the MCC scores for the top key 15 TFs. c Heatmap showing the expression of the top key 15 TFs at indicated time points during cellular reprogramming. d Normalized RNA-seq and CUT&Tag sequencing of histone modifications (H3K4me3, H3K27ac, and H3K27me3) at the genome loci of Ascl1, Olig2, Zic1, Pou3f2, and Lhx2 at the indicated time points during cellular reprogramming. Relative reprogramming efficiency, assessed by the proportion of tdTomato+ cells at day 32, following knockdown of Ascl1 (e) or Olig2 (f) at the indicated time points under M7 + M3 induction (n = 5 independent biological samples per group). The reprogramming efficiency at day 32 for M7 + M3-induced cells was set to “1” with DMSO serving as the negative control. WT, wild-type; Control KD, scramble shRNA-mediated gene knockdown. g scRCF network visualization of the putative signaling cascades induced by small molecules targeting Ascl1 and Olig2. Orange rectangles represent perturbagens, blue diamonds represent signaling protein targets, white ellipses represent intermediate signaling proteins, and green hexagons represent query TFs. Data are mean ± SD. One-way ANOVA was used to assess statistical significance. Source data are provided as a Source Data file.
