Dnmt3a regulates a core transcriptional signature correlating with HSC and self- renewal. (A) RNA-seq analysis. PCA plot representing differentially expressed (DE) gene-expression profile of the LSK cells form Jak2^VF-Cas9 and Jak2^VF-Dnmt3a-Cas9 recipients 8 weeks post-transplant. Each dot represents an individual biological replicate (mouse). (B) Heat map showing differentially expressed genes (FDR < 0.05) from Jak2^VF-Cas9, and Jak2^VF-Dnmt3a-Cas9. (C) GSEA, gene-expression signatures of LT-HSC and hematopoietic progenitor stemness genes comparing LSKs sorted from Jak2^VF-Cas9 and Jak2^VF-Dnmt3a-Cas9 recipient mice. The NES and FDR q value are indicated (top and bottom rows, respectively) on each GSEA plot. (D) GSEA for Dnmt3a mutant/KO gene-expression signatures in LSK, Cd150⁺,²³  (E) LSK,²⁴  (F) LSK,²²  (G) LSK,²⁵  and (H) AML.²⁶  NES (top), and FDR q value (bottom rows) are indicated on each GSEA plot. (I) DNMT3A gene-expression core signature based on the overlap between studies (D-H). (J) Heat map of differentially upregulated genes (FDR < 0.05) in Jak2^VF-Dnmt3a-Cas9 that are in the DNMT3A upregulated gene core.