In vivo fate mapping identifies pre-TCR? expression as an intra- and extrathymic, but not prethymic, marker of T lymphopoiesis.

ABSTRACT: Expression of the pre-T cell receptor ? (pT?) 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 pT?(iCre) knockin mouse line and performed lineage-tracing experiments to precisely quantitate the contribution of pT?-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 pT? expression as a faithful molecular marker of T lineage commitment. Specifically, the fate of pT?-expressing progenitors was found to include all ?? and most ?? 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 pT? 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.

SUBMITTER: Luche H 

PROVIDER: S-EPMC3620354 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature