Yui, Mary A. and Feng, Ni and Rothenberg, Ellen V. (2010) Fine-Scale Staging of T Cell Lineage Commitment in Adult Mouse Thymus. Journal of Immunology, 185 (1). pp. 284-293. ISSN 0022-1767 http://resolver.caltech.edu/CaltechAUTHORS:20100630-085544779
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T cell development is marked by the loss of alternative lineage choices accompanying specification and commitment to the T cell lineage. Commitment occurs between the CD4 and CD8 double-negative (DN) 2 and DN3 stages in mouse early T cells. To determine the gene regulatory changes that accompany commitment, we sought to distinguish and characterize the earliest committed wild-type DN adult thymocytes. A transitional cell population, defined by the first downregulation of surface c-Kit expression, was found to have lost the ability to differentiate into dendritic cells and NK cells when cultured without Notch-Delta signals. In the presence of Notch signaling, this subset generates T lineage descendants in an ordered precursor–product relationship between DN2, with the highest levels of surface c-Kit, and c-Kit–low DN3 cells. These earliest committed cells show only a few differences in regulatory gene expression, compared with uncommitted DN2 cells. They have not yet established the full expression of Notch-related and T cell differentiation genes characteristic of DN3 cells before β selection. Instead, the downregulation of select stem cell and non-T lineage genes appears to be key to the extinction of alternative lineage choices.
|Additional Information:||© 2010 by The American Association of Immunologists, Inc. Received for publication February 26, 2010. Accepted for publication April 25, 2010. This work was supported by National Institutes of Health Grant R01 AI064590 (to M.A.Y.), the Louis A. Garfinkle Memorial Laboratory Fund, the Al Sherman Foundation, and the Albert Billings Ruddock Professorship (to E.V.R.).|
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|Deposited By:||Tony Diaz|
|Deposited On:||03 Aug 2010 23:18|
|Last Modified:||26 Dec 2012 12:11|
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