Fig. 3: Single-cell RNA sequencing (scRNA-seq) uncovered an activated unfolded protein response in Syncrip deficient HSC populations.
A Identification of hematopoietic cell populations within WT Syncripf/f (n = 3) and KO SyncripΔ/Δ (n = 3) Lin-ckit+ cells based on UMAP analysis of Single-cell RNA sequencing (scRNA-seq). B Gene expression heat map of the highly expressed genes in hematopoietic stem cell-cluster 1 (HSC-C1), hematopoietic stem cell-cluster 1 (HSC-C2), multipotent-progenitor 1 (MPP1) and 2 (MPP2) populations. C Reconstruction of the lineage branching among of four early hematopoietic stem/progenitor cells HSC-C1, HSC-C2, MPP1 and MPP2 populations using diffusion pseudotime (DPT) analysis. D GSEA analysis of genes differentially expressed between HSC-C1 vs. HSC-C2 in WT Syncripf/f mice for enrichment of gene signatures specific for low output and high output HSC. E UMAP displays of all hematopoietic clusters of WT Syncripf/f and KO SyncripΔ/Δ scRNA-seq as described in (A). Cluster HSC-C1 shows the most shift. HSC, Ba and MEP clusters were highlighted for comparison. F Quantitative summary of frequencies of different populations defined by scRNA-seq analysis in WT Syncripf/f (n = 3) and KO SyncripΔ/Δ (n = 3). Data represent mean ± s.e.m. p values were calculated by two-tailed t test unless specified. ns not significant. G, H Volcano plots showing genes differentially expressed between Syncripf/f vs. SyncripΔ/Δ within HSC-C1 and HSC-C2 clusters. The most differentially expressed genes are highlighted. I Enrichr analysis for GO biological processes and Reactome enrichment of significant (FDR < 0.05) downregulated and upregulated genes within the HSC-C1 population of SyncripΔ/Δ vs. Syncripf/f. X-axis: -log10(p value). Enrichment of downregulated targets was depicted as negative log10(p) and enrichment of upregulated targets was depicted as positive log10(p). p-values were calculated by Fisher’s exact test. J Enrichr analysis for GO biological processes and Reactome enrichment of significant (FDR < 0.05) downregulated and upregulated genes within the HSC-C2 population of SyncripΔ/Δ vs. Syncripf/f. X-axis: -log10(p value). p-values were calculated by Fisher’s exact test. Source data are provided as Source Data File.
