Wendorff, Agnieszka A.Koch, UteWunderlich, F. ThomasWirth, SilviaDubey, ChristelleBrüning, Jens C.Macdonald, H. RobsonRadtke, Freddy2010-12-032010-12-032010-12-03201010.1016/j.immuni.2010.11.014https://infoscience.epfl.ch/handle/20.500.14299/61873WOS:000286082600007Although canonical Notch signaling regulates multiple hematopoietic lineage decisions including T cell and marginal zone B cell fate specification, the downstream molecular mediators of Notch function are largely unknown. We showed here that conditional inactivation of Hes1, a well-characterized Notch target gene, in adult murine bone marrow (BM) cells severely impaired T cell development without affecting other Notch-dependent hematopoietic lineages such as marginal zone B cells. Competitive mixed BM chimeras, intrathymic transfer experiments, and in vitro culture of BM progenitors on Delta-like-expressing stromal cells further demonstrated that Hes1 is required for T cell lineage commitment, but dispensable for Notch-dependent thymocyte maturation through and beyond the beta selection checkpoint. Furthermore, our data strongly suggest that Hes1 is essential for the development and maintenance of Notch-induced T cell acute lymphoblastic leukemia. Collectively, our studies identify Hes1 as a critical but context-dependent mediator of canonical Notch signaling in the hematopoietic system.Acute Lymphoblastic-LeukemiaBeta-Selection CheckpointHematopoietic Stem-CellsZone B-CellsDelta-Like 4In-VivoT-CellsThymocyte DevelopmentLineage CommitmentAlpha-BetaHes1 Is a Critical but Context-Dependent Mediator of Canonical Notch Signaling in Lymphocyte Development and Transformationtext::journal::journal article::research article