Fig. 1: CRISPR screen identified Clu and Cd38 as regulators of myeloid-biased hematopoiesis.
From: Clusterin drives myeloid bias in aged hematopoietic stem cells by regulating mitochondrial function
a, Volcano plot showing differentially expressed genes (DEGs) of oHSCs from old mice (24 months) compared with yHSC from young mice (2 months) (n = 3 per group; two-sided Wald test P value). b, Intersection of upregulated genes in oHSCs from our dataset and the public HSC aging signature genes (left panel). The four criteria used for inclusion (right panel). FPKM, fragments per kilobase of transcript per million mapped reads; log2FC, log2 fold change; P. adj, adjusted P value. c, Heatmap of the expression of candidates included in the CRISPR loss-of-function screen. d, Workflow of in vivo CRISPR screen in oHSCs. e, Rank plot showing screening results comparing mature B, T, and myeloid cells with sp-oHSCs. The x axis indicates the rank order of genes. The y axis indicates the gene’s robust rank aggregation (RRA) score for positive enrichment of sgRNAs. Bottom panel shows the distribution of the average fold change of three sgRNAs with the five barcodes for the top hits. Red bars indicate sgRNAs enrichment in B, T, or myeloid cells compared with sp-oHSCs for the top hits. f, Rank plot showing screening results comparing mature B or T cells with myeloid cells. The axes are the same as those in e. Red bars indicate sgRNAs enrichment in B or T cells compared with myeloid cells for the top hits. g, Rank plot showing screening results comparing mature B, T, and myeloid cells with ep-oHSCs. The axes and red bars are the same as those in e. Red bars indicate sgRNAs enrichment in B or T cells compared with ep-oHSCs for the top hits. h, Four pairwise comparisons identified Clu and Cd38 as the top hits. PB, peripheral blood; BM, bone marrow; Mye, myeloid.
