Fig. 4

Fig. 4 Transcription factors controlling differential gene expression in MG and MGPC following LD and NMDA treatment.

a Schematic of gene regulatory networks (GRNs) that direct Müller glia (MG) reprogramming and MG-derived progenitor cell (MGPC) differentiation after injury via light damage (LD) and NMDA treatment. b Inference of activator and repressor function for each individual transcription factor from multiomic datasets. The y-axis represents the correlation distribution between gene expression and chromVAR score. The top three activator and repressor TF-Motif pairs are shown on the right. The center, lower/upper bound of the boxplot shows the median, 25th and 75th of the correlations, The whiskers extend from the ends of the box to the smallest and largest values that are within 1.5 times the IQR from the lower and upper quartiles, respectively. c Gene regulatory networks of LD and NMDA datasets. (left) Triple regulons model. A circle indicates a TF, a rectangle indicates a target gene, and a diamond indicates a peak. (right) barplot shows the types of regulons between LD and NMDA datasets. d Venn diagram shows the overlap of regulons between LD and NMDA datasets. e Enriched gene regulatory networks of LD and NMDA treatment. (left) Enriched Triple regulons model for each condition. A circle indicates a TF, a rectangle indicates a target gene, and a diamond indicates a peak. Color indicates the log2 fold change of gene/peak between LD and NMDA datasets.(right) barplot shows the number of different types of regulons between LD and NMDA enriched GRNs. f An example of stat2 regulons. A circle indicates a TF, a rectangle indicates a target gene, and a diamond indicates a peak. Color indicates the log2 fold change of gene/peak between LD and NMDA datasets. g Heatmap showing the differentially expressed genes in microglia/macrophages after LD and NMDA treatment. Microglia/macrophage cells are ordered by time points after injury, and an averaged expression level is shown for each time point. Color represents mean-centered normalized expression levels. h Dotplot displays the key activator TFs for each divergent gene cluster. The color represents the ratio of the TF’s targets within that gene cluster, while the dot size indicates the p value of the TF’s regulatory specificity for the respective gene cluster. Hypergeometric test were used test whether the TF’s targets are enriched in the DEG clusters.