Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing

Nat Immunol. 2016 Jun;17(6):666-676. doi: 10.1038/ni.3412. Epub 2016 Apr 4.


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 results identify an early hematopoietic-lineage bifurcation that separates the myeloid lineages before their segregation from other hematopoietic-lineage potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cell Differentiation*
  • Cell Lineage*
  • Cells, Cultured
  • Computational Biology
  • GATA1 Transcription Factor / genetics
  • GATA1 Transcription Factor / metabolism
  • Hematopoiesis
  • Immunity, Innate
  • Lymphocytes / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Cells / physiology*
  • Myeloid Progenitor Cells / physiology*
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Tissue Array Analysis
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism


  • Antigens, CD
  • GATA1 Transcription Factor
  • Gata1 protein, mouse
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3