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According to current models of hematopoiesis, lymphoid-primed multi-potent progenitors (LMPPs) (Lin⁻Sca-1⁺c-Kit⁺CD34⁺Flt3^hi) and common myeloid progenitors (CMPs) (Lin⁻Sca-1⁺c-Kit⁺CD34⁺CD41^hi) establish an early branch point for separate lineage-commitment pathways from hematopoietic stem cells, with the notable exception that both pathways are proposed to generate all myeloid innate immune cell types through the same myeloid-restricted pre–granulocyte-macrophage progenitor (pre-GM) (Lin⁻Sca-1⁻c-Kit⁺CD41⁻FcγRII/III⁻CD150⁻CD105⁻). By single-cell transcriptome profiling of pre-GMs, we identified distinct myeloid differentiation pathways: a pathway expressing the gene encoding the transcription factor GATA-1 generated mast cells, eosinophils, megakaryocytes and erythroid cells, and a pathway lacking expression of that gene generated monocytes, neutrophils and lymphocytes. These …