Fig. 5: Multi-omics analysis identifies SYNCRIP functional targets in HSCs. | Nature Communications

Fig. 5: Multi-omics analysis identifies SYNCRIP functional targets in HSCs.

From: RNA binding protein SYNCRIP maintains proteostasis and self-renewal of hematopoietic stem and progenitor cells

Fig. 5

A Number of SYNCRIP-HyperTRIBE significant edit sites (FDR < 0.05 and differential editing frequency (SYNCRIP-ADAR vs. control) ≥ 0.1) and their genic locations in HSC and MPP cells. B Number of target genes with edited sites in (A) in hematopoietic stem cell (HSC) and multipotent progenitor (MPP). C Venn diagram of SYNCRIP target mRNAs identified in HSC and MPP: 534 shared targets, 262 HSC unique targets and 71 MPP unique targets. D De novo motif search identifies SYNCRIP-specific binding motifs enriched in mRNA targets with edited sites in both coding regions (CDS and 3’-UTR). E Probability density function (PDF) plots showing the distance from edits sites to the nearest SYNCRIP motifs as depicted. F Enrichr analysis for GO biological processes, GO molecular function, Reactome and KEGG enrichment of HSC and MPP shared SYNCRIP target genes. X-axis: -log10(p value). G Enrichr analysis for GO biological processes and Reactome enrichment of significant (FDR < 0.05) downregulated and upregulated genes in Syncrip deficient HSCs. X-axis: Enrichment of downregulated targets negative log10(p) and enrichment of upregulated targets positive log10(p. H Venn diagram of SYNCRIP target mRNAs with genes significantly (FDR < 0.05, FC≥2) upregulated (499 genes) and downregulated (n = 561) in Syncrip deficient HSCs. I, J GSEA analysis showing negative enrichment of proteins significantly downregulated for gene expression signatures upregulated in HSC vs. MPP, Cellular response to heat stress. NES-normalized enrichment score. K Venn diagram of SYNCRIP direct target mRNAs (n = 534) with mRNAs significantly downregulated ((FDR < 0.05, FC≤−2: n = 561) in Syncrip deficient HSCs and genes of which protein levels are significantly downregulated (FDR < 0.1, FC≤−2: n = 803). L Heat map depicting relative protein levels of 12 and 51 overlapping genes highlighted in (K) in SyncripΔ/Δ vs. Syncripf/f LSKs. Red boxes highlight GTPase/cytoskeleton associated targets. M Enrichr analysis for GO biological processes, molecular function, Reactome and KEGG enrichment of SYNCRIP target genes whose proteins are downregulated in Syncrip deficient LSKs. X-axis: log10(p value). Source data are provided as Source Data File. For all enricher analysis, p-values were calculated by Fisher’s exact test.

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