Ectopic expression of PRMT1 phenotypically and transcriptomically rescues dKO HSC defects. (A) Total number and composition of colonies produced by WT and dKO LSKs transduced with Empty Vector (EV) control or PRMT1. Data from 3 independent experiments are shown. (B) LTC-IC frequency from HSPCs as indicated. (C) Percentage BrdU⁺ HSPCs from indicated samples labeled overnight with BrdU analogue in vitro. Data from 3 independent experiments are shown. (D) CldU track length of fibers from HSPCs isolated from WT or dKO mice that received transplant (+EV or PRMT1). (E) Representative images of elongating fork lengths. Scale bar, 10 μm. (F) Bidirectional fork symmetry. (G) Frequency of stalled fork present in indicated samples. Fiber data from 1 representative experiment are shown (n = 3, data are shown in supplemental Figure 6). Immunofluorescent images (H) and focus counts (I) of ƳH2AX staining of indicated HSPCs. Several fields of cells were scored from 2 independent experiments. Scale bars, 25 μm. (J) Enrichment plots of stem-related gene sets in RNA-seq data sets as indicated. (K) Fold change in expression of DNA replication transcripts. (L) Gene Ontology analysis of significantly upregulated genes from HSPCs isolated from dKO mice and transduced with PRMT1 WT compared with EV (n = 433). ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗P ≤ .001; ∗∗∗∗P ≤ .0001; NS, P > .05.