Universität zu Köln

Wendorff, Agnieszka A., Koch, Ute ORCID: 0000-0001-7914-7061, Wunderlich, F. Thomas, Wirth, Silvia, Dubey, Christelle, Bruening, Jens C., MacDonald, H. Robson and Radtke, Freddy ORCID: 0000-0003-4315-4045 (2010). Hes1 Is a Critical but Context-Dependent Mediator of Canonical Notch Signaling in Lymphocyte Development and Transformation. Immunity, 33 (5). S. 671 - 685. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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Abstract

Although 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wendorff, Agnieszka A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Ute UNSPECIFIED orcid.org/0000-0001-7914-7061 UNSPECIFIED Wunderlich, F. Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirth, Silvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Dubey, Christelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED MacDonald, H. Robson UNSPECIFIED UNSPECIFIED UNSPECIFIED Radtke, Freddy UNSPECIFIED orcid.org/0000-0003-4315-4045 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-492218
DOI:	10.1016/j.immuni.2010.11.014
Journal or Publication Title:	Immunity
Volume:	33
Number:	5
Page Range:	S. 671 - 685
Date:	2010
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4180
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACUTE LYMPHOBLASTIC-LEUKEMIA; BETA-SELECTION CHECKPOINT; HEMATOPOIETIC STEM-CELLS; ZONE B-CELLS; DELTA-LIKE 4; IN-VIVO; T-CELLS; THYMOCYTE DEVELOPMENT; LINEAGE COMMITMENT; ALPHA-BETA Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49221