Lymphomyeloid Contribution of an Immune-Restricted Progenitor Emerging Prior to Definitive Hematopoietic Stem Cells

In jawed vertebrates, development of an adaptive immune-system is essential for protection of the born organism against otherwise life-threatening pathogens. Myeloid cells of the innate immune system are formed early in development, whereas lymphopoiesis has been suggested to initiate much later, following emergence of definitive hematopoietic stem cells (HSCs). Herein, we demonstrate that the embryonic lymphoid commitment process initiates earlier than previously appreciated, prior to emergence of definitive HSCs, through establishment of a previously unrecognized entirely immune-restricted and lymphoid-primed progenitor. Notably, this immune-restricted progenitor appears to first emerge in the yolk sac and contributes physiologically to the establishment of lymphoid and some myeloid components of the immune-system, establishing the lymphomyeloid lineage restriction process as an early and physiologically important lineage-commitment step in mammalian hematopoiesis. [Display omitted] •Embryonic lymphoid lineage restriction initiates prior to emergence of definitive HSC•Embryonic lymphoid-primed progenitors have immune-restricted lymphomyeloid potential•Embryonic lymphoid-primed progenitors contribute to myelo- and lymphopoiesis in utero•Lympho-myelo immune restriction is an early-fate decision in embryonic hematopoiesis An immune-restricted lymphomyeloid-primed progenitor with the capacity to contribute to both myeloid and lymphoid lineages in the developing embryo emerges prior to definitive HSCs.