Identification of two distinct pathways of human myelopoiesis.

The myeloid innate immune system plays key roles in the defence against parasites and bacteria, and carries out essential functions during tissue homeostasis and repair. It consist of neutrophils, macrophages, eosinophils, basophils and mast cells. Myelopoietic dysfunction or deregulation underlies numerous pathologies, ranging from immune deficiencies and allergies to myeloproliferative disorders and myeloid leukemia. To study malignant myelopoiesis, it is essential to understand the ontology of the different celltypes. In a generally accepted model for hematopoietic differentiation, all myeloid cells are preceded by a common granulocyte and macrophage progenitor that has the potential for all myeloid celltypes at the single cell level. However, we recently proposed a model for mouse hematopoiesis in which myeloid cells are formed via two independent pathways, one leading towards macrophages and neutrophils and one leading towards eosinophils, basophils and mast cells. The first pathway is affiliated with lymphoid potentials whereas the latter with megakaryocyte/erythroid development. Here, we demonstrate that those findings translate to human hematopoiesis. We demonstrate prospective isolation of myeloid progenitor cells that have restricted multipotent myeloid potential and are affiliated with lineages similar to those found in the mouse hierarchy. Gene expression of human single common myeloid progenitor cells (Lin- CD34+ CD38+ CD45RA- CD123+), and defined bulk populations (100 cells) within the CD34+ compartment from bone marrow of healthy adult donors.