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

Guo, Yalin and Maillard, Ivan and Chakraborti, Sankhamala and Rothenberg, Ellen V. and Speck, Nancy A. (2008) Core binding factors are necessary for natural killer cell development, and cooperate with Notch signaling during T cell specification. Blood, 112 (3). pp. 480-492. ISSN 0006-4971. PMCID PMC2481540. doi:10.1182/blood-2007-10-120261.

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CBF{beta} is the non-DNA binding subunit of the core binding factors (CBFs). Mice with reduced CBF{beta} levels display profound, early defects in T but not B cell development. Here we show that CBF{beta} 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 CBF{beta} insufficient cells, nor can overexpression of Runx1 or CBF{beta} overcome a lack of Notch signaling. Therefore the ability of the prethymic cell to respond appropriately to Notch is dependent on CBF{beta}, and both signals converge to activate the T cell developmental program.

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Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2008 by American Society of Hematology. Submitted October 29, 2007. Accepted March 13, 2008. Blood First Edition Paper, prepublished online April 4, 2008; DOI 10.1182/blood-2007-10-120261. An Inside Blood analysis of this article appears at the front of this issue. We gratefully acknowledge Juan Carlos Zúñiga-Pflücker for providing the OP9-DL1 cells, Michael Chen for the Runx1 virus, Richard Moriggl for the Stat5a cDNA, and Caroline Speck, Michael Chen, and Brandon Zeigler for technical assistance. This work was supported by NIH RO1CA075611 (N.A.S.) and the Damon Runyon Cancer Research Foundation DRG-102-05 (I.M.). Core services were supported in part by the Norris Cotton Cancer Center (NIH CA23108). Contribution: Y.G., S.C., and I.M. performed experiments; all authors analyzed the results; N.A.S., I.M, and Y.G. made the figures; all authors designed the research and wrote the paper. The authors declare no competing financial interests. The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734.
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Damon Runyon Cancer Research FoundationDRG-102-05
Issue or Number:3
PubMed Central ID:PMC2481540
Record Number:CaltechAUTHORS:GUOblo08
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10066
Deposited By: Archive Administrator
Deposited On:11 Apr 2008
Last Modified:08 Nov 2021 21:04

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