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Antagonistic regulation by the transcription factors C/EBPα and MITF specifies basophil and mast cell fates. Immunity 2013 Jul 25;39(1):97-110

Date

07/23/2013

Pubmed ID

23871207

Pubmed Central ID

PMC3755602

DOI

10.1016/j.immuni.2013.06.012

Scopus ID

2-s2.0-84880728627   62 Citations

Abstract

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.

Author List

Qi X, Hong J, Chaves L, Zhuang Y, Chen Y, Wang D, Chabon J, Graham B, Ohmori K, Li Y, Huang H

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

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