An Early T Cell Lineage Commitment Checkpoint Dependent on the Transcription Factor Bcl11b
- Creators
- Li, Long
- Leid, Mark
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Rothenberg, Ellen V.
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.
Additional Information
© 2010 American Association for the Advancement of Science. Received 2 March 2010; accepted 19 May 2010. We thank P. Liu, H. Kawamoto, P. Li, T. Ikawa, D. Scripture-Adams, and members of the Rothenberg lab for sharing unpublished results and helpful discussion; D. Metzger and J.-M. Bornert for help with generation of the floxed Bcl11b mice; H.-Y. Kueh for guidance in data analysis; T. Taghon and F. Costantini for vectors and mice; D. Perez and R. Diamond for flow cytometry support; and R. Butler and S. Washburn for animal care and breeding supervision. Supported by a California Institute for Regenerative Medicine fellowship (L.L.), NIH grants R33 HL089123 and RC2 CA148278 (E.V.R.), NIH grant R01 GM60852 (M.L.), the Caltech–City of Hope Biomedical Initiative, the Louis Garfinkle Memorial Laboratory Fund, the Al Sherman Foundation, and the A. B. Ruddock Professorship.Attached Files
Accepted Version - nihms231731.pdf
Supplemental Material - 1.pdf
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Additional details
- PMCID
- PMC2935300
- Eprint ID
- 19103
- DOI
- 10.1126/science.1188989
- Resolver ID
- CaltechAUTHORS:20100719-105902148
- California Institute for Regenerative Medicine (CIRM)
- NIH
- R33 HL089123
- NIH
- RC2 CA148278
- NIH
- R01 GM60852
- Caltech-City of Hope Biomedical Initiative
- Louis Garfinkle Memorial Laboratory Fund
- Al Sherman Foundation
- Albert Billings Ruddock Professorship
- Created
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2010-08-05Created from EPrint's datestamp field
- Updated
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2021-11-08Created from EPrint's last_modified field