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 (II7r) Cre recombinase knockin mice and traced lymphocyte development by visualizing the history of II7r expression. II7r fate mapping labeled all T cells but few myeloid cells. More than 85% of T cell progenitors were II7r reporter + and, hence, had arisen from an II7r-expressing pathway. In contrast, the overwhelming majority of myeloid cells in the thymus were derived from II7r 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.