title: Antagonistic regulation by the transcription factors C/EBPα and MITF specifies basophil and mast cell fates.
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.
authors.affiliation: Department of Medicine, Division of Allergy and Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Qi
authors.forename: Jessie
authors.initials: J
authors.lastname: Hong
authors.forename: Lee
authors.initials: L
authors.lastname: Chaves
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Demin
authors.initials: D
authors.lastname: Wang
authors.forename: Jacob
authors.initials: J
authors.lastname: Chabon
authors.forename: Brian
authors.initials: B
authors.lastname: Graham
authors.forename: Keitaro
authors.initials: K
authors.lastname: Ohmori
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D001491:Basophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D051739:Microphthalmia-Associated Transcription Factor; D050799:STAT5 Transcription Factor