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
07/23/2013Pubmed ID
23871207Pubmed Central ID
PMC3755602DOI
10.1016/j.immuni.2013.06.012Scopus ID
2-s2.0-84880728627 (requires institutional sign-in at Scopus site) 107 CitationsAbstract
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 HAuthor
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBasophils
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