First Author | Luche H | Year | 2013 |
Journal | J Exp Med | Volume | 210 |
Issue | 4 | Pages | 699-714 |
PubMed ID | 23509324 | Mgi Jnum | J:197923 |
Mgi Id | MGI:5494902 | Doi | 10.1084/jem.20122609 |
Citation | Luche H, et al. (2013) In vivo fate mapping identifies pre-TCRalpha expression as an intra- and extrathymic, but not prethymic, marker of T lymphopoiesis. J Exp Med 210(4):699-714 |
abstractText | Expression of the pre-T cell receptor alpha (pTalpha) gene has been exploited in previous studies as a molecular marker to identify tiny cell populations in bone marrow (BM) and blood that were suggested to contain physiologically relevant thymus settling progenitors (TSPs). But to what extent these cells genuinely contribute to thymopoiesis has remained obscure. We have generated a novel pTalpha(iCre) knockin mouse line and performed lineage-tracing experiments to precisely quantitate the contribution of pTalpha-expressing progenitors to distinct differentiation pathways and to the genealogy of mature hematopoietic cells under physiological in vivo conditions. Using these mice in combination with fluorescent reporter strains, we observe highly consistent labeling patterns that identify pTalpha expression as a faithful molecular marker of T lineage commitment. Specifically, the fate of pTalpha-expressing progenitors was found to include all alphabeta and most gammadelta T cells but, in contrast to previous assumptions, to exclude B, NK, and thymic dendritic cells. Although we could detect small numbers of T cell progenitors with a history of pTalpha expression in BM and blood, our data clearly exclude these populations as physiologically important precursors of thymopoiesis and indicate that they instead belong to a pathway of T cell maturation previously defined as extrathymic. |