Antagonistic regulation by the transcription factors C/EBPα and MITF specifies basophil and mast cell fates

Immunity. 2013 Jul 25;39(1):97-110. doi: 10.1016/j.immuni.2013.06.012. Epub 2013 Jul 18.


It remains unclear whether basophils and mast cells are derived from a common progenitor. Furthermore, how basophil versus mast cell fate is specified has not been investigated. Here, we have identified a population of granulocyte-macrophage progenitors (GMPs) that were highly enriched in the capacity to differentiate into basophils and mast cells while retaining a limited capacity to differentiate into myeloid cells. We have designated these progenitor cells "pre-basophil and mast cell progenitors" (pre-BMPs). STAT5 signaling was required for the differentiation of pre-BMPs into both basophils and mast cells and was critical for inducing two downstream molecules: C/EBPα and MITF. We have identified C/EBPα as the critical basophil transcription factor for specifying basophil cell fate and MITF as the crucial transcription factor for specifying mast cell fate. C/EBPα and MITF silenced each other's transcription in a directly antagonistic fashion. Our study reveals how basophil and mast cell fate is specified.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basophils / cytology
  • Basophils / immunology*
  • Basophils / metabolism
  • Blotting, Western
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / immunology*
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Cells, Cultured
  • Flow Cytometry
  • Gene Expression Profiling
  • Granulocyte-Macrophage Progenitor Cells / cytology
  • Granulocyte-Macrophage Progenitor Cells / immunology
  • Granulocyte-Macrophage Progenitor Cells / metabolism
  • HEK293 Cells
  • Humans
  • Mast Cells / cytology
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / immunology*
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Oligonucleotide Array Sequence Analysis
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / immunology
  • STAT5 Transcription Factor / metabolism
  • Stem Cells / immunology
  • Stem Cells / metabolism


  • CCAAT-Enhancer-Binding Protein-alpha
  • Microphthalmia-Associated Transcription Factor
  • STAT5 Transcription Factor

Associated data

  • GEO/GSE41596