Common Developmental Pathway for Primitive Erythrocytes and Multipotent Hematopoietic Progenitors in Early Mouse Development

• Primitive erythrocytes and lymphomyeloid progenitors have bipotent precursors
• The precursors form primitive erythroid and lymphomyeloid cells in distinct waves
• The common precursors are noted in the yolk sac and embryo proper
• Primitive erythrocytes and lymphocytes can be derived from a single precursor cell

SummaryDevelopment of the hematopoietic system proceeds in a multistep manner. Primitive erythrocytes are the first hematopoietic cells to be observed that were produced transiently in developing embryos. Multilineage lymphohematopoiesis occurs after the primitive erythropoiesis. However, the lineage relationship of cells that comprise embryonic hematopoietic system is not well characterized. To clarify this process, careful analyses of the embryonic cells that differentiate into these cell lineages are necessary. We identified the common precursors of primitive erythrocytes and multipotent hematopoietic cells in mouse embryonic stem cell cultures and mouse embryos. A subset defined as CD45−CD41+AA4.1− cells showed bipotential capability to produce primitive erythrocytes and lymphomyeloid cells at the single-cell level. The cell population was present in vivo before hematopoietic stem cells (HSCs) appeared. Our results show that primitive erythrocytes and lymphomyeloid cells are not completely separate cell lineages, and these precursors comprise the embryonic hematopoietic system before HSC emergence.