Extended Data Fig. 5: Fli-1 deficient HSPCs exhibit defusing of activation programs and parallel induction of Spi1-mediated quiescence programs.

a, BETA motif analysis on Fli-1 target genes downregulated in Fli-1^ROSAΔ HSPCs, showing the top scored motifs (upper panel) and the top scored motif for Fli-1 target genes vs. non-targeted genes downregulated in Fli-1^ROSAΔ HSPCs (lower panel). b, BETA activating/repressive function prediction analysis of the Spi1 binding data sets from in vivo sorted dormant HSPCs and expression data sets from Fli-1^ROSAΔ vs. WT HSPCs, identifying upregulated (red) and downregulated (purple) genes. The dashed line indicates the non-differentially expressed genes as background. c, d, GSEA analysis plot for HSC quiescence (c) and HSC activation (d) factors expression in Fli-1^ROSAΔ vs. WT HSPCs, showing a positive enrichment for quiescence factors and negative enrichment for activation factors in Fli-1^ROSAΔ HSPCs. e, Heatmap for selected HSC quiescence (upper panel) and HSC activation (lower panel) factors across RNA-seq replicates of Fli-1^ROSAΔ and WT HSPCs. Scale bar and coloring represent the Z-score scaled by gene for Log counts per 10⁶ normalized by library size (trimmed mean of M-values). f, Bars displaying the number of predicted active enhancers, following activity-by-contact (ABC) model analysis, per each quiescence factor for WT (lower panel) and Fli-1^ROSAΔ (upper panel) HSPCs. Also, presenting a heatmap for the averaged ABC PowerLaw score for the predicted enhancers per quiescence factor in WT and Fli-1^ROSAΔ HSPCs. g, Frequency of cycling HSPCs in co-culture as determined by flow cytometry on day 4 post 4-OHT induction. Unpaired two tailed t-test was used; n = 5 per WT or Fli-1^SCLΔ. Data are presented as mean values +/- SEM. h, IGV peaks plots for the genomic loci of Spi1 (left) and Fli-1 (right), displaying bigWig coverage tracks for WT and Fli-1^ROSAΔ ATAC-seq, H3K27ac-ChIP-seq, Fli1-ChIP-seq, and Spi1-ChIP-seq.

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