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 α ( 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. ► Il7r mRNA is expressed in bone marrow lymphoid progenitors, but not in pro T cells ► Il7r Cre recombinase reveals past and current expression of Il7r (fate mapping) ► Fate mapping shows that most pro T cells arise from Il7r + lymphoid-primed progenitors ► The vast majority of myeloid cells in the thymus arise from Il7r − progenitors