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DELAY identifies ybx1 as a global transcriptional regulator upstream of atoh1a. (A) A t-SNE embedding depicts scRNA-seq data from Baek et al. (2022) containing HC progenitors, young HCs, mature HCs, central SCs, dorsoventral (DV) SCs, anteroposterior (AP) SCs, amplifying SCs and mantle cells during homeostasis and 0, 0. 5, 1, 3, 5, and 10 hpa. (B) Two pseudotime trajectories depict central SC and HC regeneration from 0-10 hpa. (C) A bubble plot shows key TFs in the combined DELAY GRN for HC and central SC regeneration. Bubble size represents outdegree centrality. (D) The expression of key TFs is depicted using generalized additive models fitted to cells’ timepoints from 0–5 hpa. The expression of ybx1 precedes that of atoh1a. (E) A dot plot shows that ybx1 is expressed across all cell types and timepoints but is relatively enriched across HC progenitors and young HCs at 3–5 hpa. The analysis in (A–E) is based on data from Baek et al., (2022). (F) Relative enrichment of bipartite motifs suggests that Ybx1 regulates transcription of its targets proximally to their transcription start sites (TSSs). (G) Two-thirds of 303 TFs in the combined GRN are predicted targets of ybx1 and possess ≥1 bipartite Ybx1 motif in their enhancers. (H) Alignment of atoh1a revealed a candidate regeneration-responsive promoter element with two Ybx1 DNA-binding sites and a 5′ UTR element with Ybx1 RNA-binding and internal ribosome entry (IRE) sites. Cyprinid species also lack proximal C-sites (C1) for Notch-mediated suppression of atoh1a transcription (Abdolazimi, Stojanova & Segil, 2016). rc, reverse complement.
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