Antagonistic Regulation by the Transcription Factors C/EBPα and MITF Specifies Basophil and Mast Cell Fates

• We have identified a population of pre-basophil and mast cell progenitors
• STAT5 signaling induces both basophil and mast cell fate determinants
• C/EBPα specifies the basophil fate whereas MITF determines the mast cell fate
• C/EBPα and MITF silence each other’s transcription in an antagonistic fashion

SummaryIt 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.

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