ArrayExpress Uploaderarrayexpress_sidmousewild-type GFP-wild-type GFPhighNras GFP-Nras GFPhighwild-type GFP-wild-type GFPhighNras GFP-Nras GFPhighwild-type GFP-wild-type GFPhighNras GFP-Nras GFPhigh720806Pre-leukemic mutations are thought to promote clonal expansion of hematopoietic stem cells (HSCs) by increasing self-renewal and...24284627E-GEOD-45194/profile/8773/arrayexpressuploader112bonecelldiseaseleukemiamyeloproliferative diseaseDec.12, 2014Falseoncogenic-nras-has-a-bimodal-effect-on-hematopoietE-GEOD-45194_A-AFFY-45Oncogenic Nras has a bimodal effect on hematopoietic stem cells promoting proliferation and self-renewalNov.12, 2014Pre-leukemic mutations are thought to promote clonal expansion of hematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness. However, mutations that increase HSC proliferation tend to reduce competitiveness and self-renewal potential, raising the question of how a mutant HSC can sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent in human myeloproliferative disease and leukemia. Here we show that a single allele of oncogenic NrasG12D increases HSC proliferation but also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all without immortalizing HSCs or causing leukemia in our experiments. NrasG12D also confers long-term self-renewal potential upon multipotent progenitors. To explore the mechanism by which NrasG12D promotes HSC proliferation and self-renewal we assessed HSC cell cycle kinetics using H2B-GFP label retention. We found that NrasG12D had a bimodal effect on HSCs, increasing the proliferation of some HSCs while increasing the quiescence and competitiveness of other HSCs. One signal can therefore increase HSC proliferation, competitiveness, and self-renewal through a bimodal effect that promotes proliferation in some HSCs and quiescence in others. 12 RNA samples from mouse bone marrows were analyzed. There are three biological replicates for each subtype.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-45194http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-45194/samples/