PASADENA, Calif.When does a cell decide its particular identity? According to biologists at the California Institute of Technology (Caltech), in the case of T cellsimmune system cells that help destroy invading pathogensthe answer is when the cells begin expressing a particular gene called Bcl11b.
The activation of Bcl11b is a "clean, nearly perfect indicator of when cells have decided to go on the T-cell pathway," says Ellen Rothenberg, the Albert Billings Ruddock Professor of Biology at Caltech and senior author of a paper about the discovery that appears in the July 2 issue of the journal Science. The paper, coauthored by Caltech postdoctoral scholar Long Li, is one of three in the issue to examine this powerful gene.
The Bcl11b gene produces what is known as a transcription factora protein that controls the activity of other genes. Specifically, the gene is a repressor, which means it shuts off other genes. This is crucial for T cells, because T cells are derived from multipotent hematopoietic stem cellsstem cells that express a wide variety of genes and have the capacity to differentiate into a host of other blood cell types, including the various cells of the immune system.
"Stem cells and their multipotent descendents follow one set of growth rules, and T cells another," says Rothenberg, "so if T-cell precursors don't give up certain stem-cell functions, bad things happen." Like stem cells, T cells have a remarkable ability to growbut as part of their T-cell-ness, she says, they do so "under incredibly strict regulation. Their growth is restricted unless certain conditions are met." The cells need to shift their growth-control rules during development; after development, because they still need to grow, the cells and their daughters need an active mechanism to make the change irreversible. Bcl11b is a long-sought part of that mechanism.
"For cells that never divide again, maintaining identity is trivial. What t
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California Institute of Technology