GATA2 is critical for mast cell differentiation and maintenance

Abstract The 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 mast cell differentiation and maintenance have not been delineated. We identified GATA2 is essential for pre-basophil and mast cell progenitors (pre-BMPs) to differentiate into mast cells. We found that GATA2 is critical in maintaining the expression of a wide range of genes that are important for performing mast cell functions. To determine the in vivo role of GATA2 in mast cell development, we generated connective tissue mast cell-specific Gata2 deficient mice. We found that Gata2 was required for connective tissue mast cell development. These mice failed to develop IgE-mediated anaphylaxis. GATA2 regulated the expression of Hdc gene, which is critical for IgE-mediated anaphylaxis, by binding to regulatory regions of the Hdc gene to promote its transcription. Our study reveals GATA2 is critical for mast cell differentiation and maintenance.