Gene expression profiling in pre-leukemic hematopoietic stem cells carrying both NrasG12D/+ and Tet2+/- mutations

By using a genetically accurate mouse model, we demonstrate that endogenous expression of oncogenic N-RasG12D and Tet2 haploinsufficiency collaborate to accelerate CMML development in mice. Gene expression was compared across all genotypes (WT, Tet2+/-, NrasG12D/+ and double mutants) in bone marrow-derived hematopoietic stem cells (CD150+CD48-Lin-Sca1+cKit+) using RNA-seq. N-RasG12D and Tet2 haploinsufficiency cooperate to induce both unique and overlapping effects on HSC gene expression programs. Gene expression profiling in FACS-sorted SLAM HSCs from 10-12 week old wild type control (n=3), NrasG12D/+ single mutant (n=3), Tet2+/- single mutant (n=3) and NrasG12D/+;Tet2+/- double mutant (n=3) mice.