Expression data from RUNX1S291fs-mutant and/or Ezh2 conditional knockout Lineage-c-Kit+Sca-1+ (LSK) cells

Recent studies have showed that loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2, are often associated with RUNX1 mutations in myelodysplastic syndrome (MDS) patients. We established a novel MDS model mouse by transducing a RUNX1S291fs mutant in hematopoietic stem cells followed by deletion of Ezh2 and found that Ezh2 loss significantly promoted RUNX1S291fs-induced MDS. We retrovirally transduced RUNX1S291fs or empty-control into either Cre-ERT;Ezh2wt/wt or Cre-ERT;Ezh2flox/flox (CD45.2+) HSCs. The transduced cells were transplanted into lethally irradiated recipient mice together with life-saving CD45.1+ wild-type bone marrow cells. After deletion of Ezh2, gene expression analysis were performed on pooled bone marrow LSK cells isolated from WT, Ezh2Δ/Δ, RUNX1S291fs, and RUNX1S291fs/Ezh2Δ/Δ mice (n=2-4) and two distinct RUNX1S291fs/Ezh2Δ/Δ-MDS mouse.