The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential.
Luc S., Luis TC., Boukarabila H., Macaulay IC., Buza-Vidas N., Bouriez-Jones T., Lutteropp M., Woll PS., Loughran SJ., Mead AJ., Hultquist A., Brown J., Mizukami T., Matsuoka S., Ferry H., Anderson K., Duarte S., Atkinson D., Soneji S., Domanski A., Farley A., Sanjuan-Pla A., Carella C., Patient R., de Bruijn M., Enver T., Nerlov C., Blackburn C., Godin I., Jacobsen SE.
The stepwise commitment from hematopoietic stem cells in the bone marrow to T lymphocyte-restricted progenitors in the thymus represents a paradigm for understanding the requirement for distinct extrinsic cues during different stages of lineage restriction from multipotent to lineage-restricted progenitors. However, the commitment stage at which progenitors migrate from the bone marrow to the thymus remains unclear. Here we provide functional and molecular evidence at the single-cell level that the earliest progenitors in the neonatal thymus had combined granulocyte-monocyte, T lymphocyte and B lymphocyte lineage potential but not megakaryocyte-erythroid lineage potential. These potentials were identical to those of candidate thymus-seeding progenitors in the bone marrow, which were closely related at the molecular level. Our findings establish the distinct lineage-restriction stage at which the T cell lineage-commitment process transits from the bone marrow to the remote thymus.