First Author | Yui MA | Year | 2010 |
Journal | J Immunol | Volume | 185 |
Issue | 1 | Pages | 284-93 |
PubMed ID | 20543111 | Mgi Jnum | J:161594 |
Mgi Id | MGI:4460019 | Doi | 10.4049/jimmunol.1000679 |
Citation | Yui MA, et al. (2010) Fine-scale staging of T cell lineage commitment in adult mouse thymus. J Immunol 185(1):284-93 |
abstractText | 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 beta selection. Instead, the downregulation of select stem cell and non-T lineage genes appears to be key to the extinction of alternative lineage choices. |