title: The STAT5-GATA2 pathway is critical in basophil and mast cell differentiation and maintenance.
abstract: Transcription factor GATA binding protein 2 (GATA2) plays critical roles in hematopoietic stem cell survival and proliferation, granulocyte-monocyte progenitor differentiation, and basophil and mast cell differentiation. However, precise roles of GATA2 in basophil and mast cell differentiation and maintenance have not been delineated. We have identified GATA2 as an essential transcription factor in differentiation of newly identified common basophil and mast cell progenitors into basophils and mast cells. We observed Gata2 haploinsufficiency for mast cell differentiation, but not for basophil differentiation. We examined the precise role of GATA2 in maintaining the expression of a wide range of genes that are important for performing basophil or mast cell functions. The effects of GATA2 on gene expression were broadly based. We demonstrated that GATA2 was required for maintaining Fcer1a mRNA and FcεRIα protein expression on both basophils and mast cells, as well as for maintaining Kit mRNA and c-Kit protein expression on mast cells. GATA2 was required for histamine synthesis and was also critical for Il4 mRNA expression in basophils and Il13 mRNA expression in mast cells. We demonstrate a STAT5-GATA2 connection, showing that the STAT5 transcription factor directly bound to the promoter and an intronic region of the Gata2 gene. Overexpression of the Gata2 gene was sufficient to direct basophil and mast cell differentiation in the absence of the Stat5 gene. Our study reveals that the STAT5-GATA2 pathway is critical for basophil and mast cell differentiation and maintenance.
authors: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors: Yapeng
authors: Y
authors: Li
authors: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors: Xiaopeng
authors: X
authors: Qi
authors: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; and.
authors: Bing
authors: B
authors: Liu
authors: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, CO 80206 huangh@njhealth.org.
authors: Hua
authors: H
authors: Huang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001491:Basophils / Q000166:cytology* / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D057895:Haploinsufficiency; D006632:Histamine / Q000096:biosynthesis; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D017455:Receptors, IgE / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D050989:GATA2 Transcription Factor; D017455:Receptors, IgE; D050799:STAT5 Transcription Factor; D006632:Histamine; D019009:Proto-Oncogene Proteins c-kit