Figure 3.

Transcriptomic and epigenomic signatures of blasts in younger patients. (A) Heatmap for differentially expressed genes [abs(log₂[FC]) >0.5 and FDR <0.05] of blasts arrested at various B-cell developmental stages between younger (<6 months old) and older (>6 months old) patients. DEGs were pooled and clustered by k-means clustering (k = 5) based on their log₂FC. Number of genes in each cluster is indicated in the parenthesis. Nonsignificant genes are colored gray. (B) Pathway enrichment analysis results for DEGs in clusters 1 (top panel) and cluster 5 (bottom panel). (C) Heatmap for differential TF motif accessibility of blasts arrested at various B-cell developmental stages between younger and older patients. For each TF in each cell, the motif accessibility at scATAC-Seq peaks was computed as the normalized deviation score using chromVAR. Color in the heatmap indicates the difference in normalized chromVAR deviation scores averaged across all cells in younger vs older patients. TFs with differential accessibility between younger and older patients were identified by Wilcoxon test of the normalized deviation scores between the 2 groups with an FDR cutoff <0.05. Nonsignificant TFs were colored in gray. (D-E) Viability of wild type and NR3C1/KLF9 KO KOPN8 (D) and SEMK2 (E) cell lines after dexamethasone treatment with different doses. Error bar, standard deviation of 2 biological replicates. P values by Student t-test for KO vs control are shown: *P < .05; **P < .01; ***P < .001. n.s., not significant.