An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b.
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.
Li
Long
L
Division of Biology 156-29, California Institute of Technology, Pasadena, CA 91125, USA.
Leid
Mark
M
Rothenberg
Ellen V
EV
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D015536:Down-Regulation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D019676:Genes, T-Cell Receptor delta; D019675:Genes, T-Cell Receptor gamma; D007694:Killer Cells, Natural / Q000166:cytology / Q000502:physiology; D038041:Lymphopoiesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
C511143:Bcl11b protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051880:Receptors, Notch; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins