ArrayExpress Uploader0mouseLineage negative, c-Kit and Sca1 (LSK) positive expressing bone marrow progenitorsWTLineage negative, c-Kit and Sca1 (LSK) positive expressing bone marrow progenitorsWTLineage negative, c-Kit and Sca1 (LSK) positive expressing bone marrow progenitorsTet2 KOLineage negative, c-Kit and Sca1 (LSK) positive expressing bone marrow progenitorsTet2 KOLineage negative, c-Kit positive and Sca1 (LSK) negative FCgammaReceptor Low CD34 positive expressing bone marrow progenitors CMPWTLineage negative, c-Kit positive and Sca1 (LSK) negative FCgammaReceptor Low CD34 positive expressing bone marrow progenitors CMPWTLineage negative, c-Kit positive and Sca1 (LSK) negative FCgammaReceptor Low CD34 positive expressing bone marrow progenitors CMPTet2 KOLineage negative, c-Kit positive and Sca1 (LSK) negative FCgammaReceptor Low CD34 positive expressing bone marrow progenitors CMPTet2 KOLineage negative, c-Kit positive and Sca1 (LSK) negative FCgammaReceptor High CD34 positive expressing bone marrow progenitors GMPWTLineage negative, c-Kit positive and Sca1 (LSK) negative FCgammaReceptor High CD34 positive expressing bone marrow progenitors GMPWTLineage negative, c-Kit positive and Sca1 (LSK) negative FCgammaReceptor High CD34 positive expressing bone marrow progenitors GMPTet2 KOLineage negative, c-Kit positive and Sca1 (LSK) negative FCgammaReceptor High CD34 positive expressing bone marrow progenitors GMPTet2 KOTet2 deficient CD150+ sorted LSKsTet2 KOTet2 deficient CD150+ sorted LSKsTet2 KO6398arrayexpress_sid6Recurrent somatic mutations in TET2 and in other genes that regulate the epigenetic state have been identified in patients with myeloid...E-GEOD-27816/profile/8773/arrayexpressuploader214cellchromatingenomeleukemiastem cellDec.12, 2014Falsetet2-loss-leads-to-increased-hematopoietic-stem-ceE-GEOD-27816_A-AFFY-45Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformationNov.11, 2014Recurrent somatic mutations in TET2 and in other genes that regulate the epigenetic state have been identified in patients with myeloid malignancies and in other cancers. However, the in vivo effects of Tet2 loss have not been delineated. We report here that Tet2 loss leads to increased stem-cell self-renewal and to progressive stem cell expansion. Consistent with human mutational data, Tet2 loss leads to myeloproliferation in vivo, notable for splenomegaly and monocytic proliferation. In addition, haploinsufficiency for Tet2 confers increased self-renewal and myeloproliferation, suggesting that the monoallelic TET2 mutations found in most TET2-mutant leukemia patients contribute to myeloid transformation. This work demonstrates that absent or reduced Tet2 function leads to enhanced stem cell function in vivo and to myeloid transformation. These studies show that a ubiquitin ligase-substrate pair can orchestrate the molecular program of HSC differentitiation Gene expression profiles from WT and Tet2-/- sorted LSK and myeloid progenitors (CMP and GMP) were compared using genome wide mRNA expression profiling by Affymetrix genechip arrays (Mouse 430 2.0) and key targets were validated by chromatin immunoprecipitation experiments.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-27816http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-27816/samples/