Fate mapping reveals separate origins of T cells and myeloid lineages in the thymus

The cellular differentiation pathway originating from the bone marrow leading to early T lymphocytes remains poorly understood. The view that T cells branch off from a lymphoid-restricted pathway has recently been challenged by a model proposing a common progenitor for T cell and myeloid lineages. We generated interleukin-7 receptor alpha (Il7r) Cre recombinase knockin mice and traced lymphocyte development by visualizing the history of Il7r expression. Il7r fate mapping labeled all T cells but few myeloid cells. More than 85% of T cell progenitors were Il7r reporter(+) and, hence, had arisen from an Il7r-expressing pathway. In contrast, the overwhelming majority of myeloid cells in the thymus were derived from Il7r reporter(-) cells. Thus, lymphoid-restricted progenitors are the major route to T cells, and distinct origins of lymphoid and myeloid lineages represent a fundamental hallmark of hematopoiesis.