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The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells
Stephen J Loughran1,2,3, Elizabeth A Kruse1,3, Douglas F Hacking1,4, Carolyn A de Graaf1,3, Craig D Hyland2, Tracy A Willson1, Katya J Henley1, Sarah Ellis5, Anne K Voss1, Donald Metcalf2, Douglas J Hilton1,3,6, Warren S Alexander2,3,6 & Benjamin T Kile1,3,6
Ets-related gene (ERG), which encodes a member of the Ets family of transcription factors, is a potent oncogene. Chromosomal rearrangements involving ERG are found in acute myeloid leukemia, acute lymphoblastic leukemia, Ewing's sarcoma and more than half of all prostate cancers; however, the normal physiological function of Erg is unknown. We did a sensitized genetic screen of the mouse for regulators of hematopoietic stem cell function and report here a germline mutation of Erg. We show that Erg is required for definitive hematopoiesis, adult hematopoietic stem cell function and the maintenance of normal peripheral blood platelet numbers.