{"owner": "ArrayExpress Uploader", "ownerprofile_id": "arrayexpress_sid", "species": "mouse", "factors": [{"GSM1098796": {"GENOTYPE": "wild-type GFP-"}}, {"GSM1098797": {"GENOTYPE": "wild-type GFPhigh"}}, {"GSM1098798": {"GENOTYPE": "Nras GFP-"}}, {"GSM1098799": {"GENOTYPE": "Nras GFPhigh"}}, {"GSM1098796": {"GENOTYPE": "wild-type GFP-"}}, {"GSM1098797": {"GENOTYPE": "wild-type GFPhigh"}}, {"GSM1098798": {"GENOTYPE": "Nras GFP-"}}, {"GSM1098799": {"GENOTYPE": "Nras GFPhigh"}}, {"GSM1098796": {"GENOTYPE": "wild-type GFP-"}}, {"GSM1098797": {"GENOTYPE": "wild-type GFPhigh"}}, {"GSM1098798": {"GENOTYPE": "Nras GFP-"}}, {"GSM1098799": {"GENOTYPE": "Nras GFPhigh"}}], "id": 7208, "pop_total": 0, "platform": 6, "summary_wrapped": "Pre-leukemic mutations are thought to promote clonal expansion of hematopoietic stem cells (HSCs) by increasing self-renewal and...", "pubmed_id": 24284627, "geo_gse_id": "E-GEOD-45194", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 1, "sample_count": 12, "tags": ["bone", "cell", "disease", "leukemia", "myeloproliferative disease"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "oncogenic-nras-has-a-bimodal-effect-on-hematopoiet", "geo_id_plat": "E-GEOD-45194_A-AFFY-45", "name": "Oncogenic Nras has a bimodal effect on hematopoietic stem cells promoting proliferation and self-renewal", "created": "Nov.12, 2014", "summary": "Pre-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.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-45194", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-45194/samples/"}