Negotiation of the T lineage fate decision by transcription-factor interplay and microenvironmental signals.
Notch-Delta signaling of hematopoietic precursors sets in motion a train of events that activates expression of T lineage genes. Even so, through many cell generations the pro-T cells remain uncommitted to the T cell fate, preserving alternative potentials as divergent as monocyte or dendritic cell fates. This plasticity can be explained by the tenacious expression of stem- and progenitor-associated regulatory genes in the cells, and by the combinatorial coding of T cell identity by factors that are not intrinsically T lineage specific in their spectra of activity. T lineage developmental success depends on precise temporal and quantitative regulation of these factors and on the continuing modulating influence of Notch-Delta signals that buffer the cells against mechanisms promoting non-T outcomes. An additional mechanism, still not fully defined, is required just prior to T cell receptor-mediated selection to end plasticity and make T lineage commitment irreversible.
Rothenberg
Ellen V
EV
Division of Biology 156-29, California Institute of Technology, Pasadena, CA 91125, USA. evroth@its.caltech.edu
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; C064045:delta protein