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Science 329 (5987): 89-93

Copyright © 2010 by the American Association for the Advancement of Science

An Early T Cell Lineage Commitment Checkpoint Dependent on the Transcription Factor Bcl11b

Long Li,1 Mark Leid,2 Ellen V. Rothenberg1,*

Abstract: The identities of the regulators that mediate commitment of hematopoietic precursors to the T lymphocyte lineage have been unknown. The last stage of T lineage commitment in vivo involves mechanisms to suppress natural killer cell potential, to suppress myeloid and dendritic cell potential, and to silence the stem cell or progenitor cell regulatory functions that initially provide T cell receptor–independent self-renewal capability. The zinc finger transcription factor Bcl11b is T cell–specific in expression among hematopoietic cell types and is first expressed in precursors immediately before T lineage commitment. We found that Bcl11b is necessary for T lineage commitment in mice and is specifically required both to repress natural killer cell–associated genes and to down-regulate a battery of stem cell or progenitor cell genes at the pivotal stage of commitment.

1 Division of Biology 156-29, California Institute of Technology, Pasadena, CA 91125, USA.
2 Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331, USA.

* To whom correspondence should be addressed. E-mail: evroth{at}its.caltech.edu

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