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 Blood, 1 August 2008, Vol. 112, No. 3, pp. 480-492.
Prepublished online as a Blood First Edition Paper on April 4, 2008; DOI 10.1182/blood-2007-10-120261.

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PLENARY PAPER

Core binding factors are necessary for natural killer cell development and cooperate with Notch signaling during T-cell specification

Yalin Guo1, Ivan Maillard2, Sankhamala Chakraborti1, Ellen V. Rothenberg3, and Nancy A. Speck1

1 Department of Biochemistry, Dartmouth Medical School, Hanover, NH; 2 Division of Hematology-Oncology, Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor; and 3 Division of Biology, California Institute of Technology, Pasadena

CBFβ is the non-DNA binding subunit of the core binding factors (CBFs). Mice with reduced CBFβ levels display profound, early defects in T-cell but not B-cell development. Here we show that CBFβ is also required at very early stages of natural killer (NK)–cell development. We also demonstrate that T-cell development aborts during specification, as the expression of Gata3 and Tcf7, which encode key regulators of T lineage specification, is substantially reduced, as are functional thymic progenitors. Constitutively active Notch or IL-7 signaling cannot restore T-cell expansion or differentiation of CBFβ insufficient cells, nor can overexpression of Runx1 or CBFβ overcome a lack of Notch signaling. Therefore, the ability of the prethymic cell to respond appropriately to Notch is dependent on CBFβ, and both signals converge to activate the T-cell developmental program.


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Related Article in Blood Online:

Exposing the core of early thymopoiesis
Stephen L. Nutt
Blood 2008 112: 454. [Full Text] [PDF]





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