LymphedemaV1, Main, Exploration, bibRecord, 001737

The STAT5-GATA2 Pathway Is Critical in Basophil and Mast Cell Differentiation and Maintenance

Identifieur interne : 001737 ( Main/Exploration ); précédent : 001736; suivant : 001738

The STAT5-GATA2 Pathway Is Critical in Basophil and Mast Cell Differentiation and Maintenance

Auteurs : Yapeng Li [États-Unis] ; Xiaopeng Qi [États-Unis] ; Bing Liu [États-Unis, République populaire de Chine] ; Hua Huang [États-Unis]

Source :

Journal of immunology (Baltimore, Md. : 1950) [ 0022-1767 ] ; 2015.

RBID : PMC:4405376

Abstract

Transcription factor GATA2 plays critical roles in hematopoietic stem cell survival and proliferation, GMP 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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405376

DOI: 10.4049/jimmunol.1500018
PubMed: 25801432
PubMed Central: 4405376

Affiliations:

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<front><div type="abstract" xml:lang="en"><p id="P1">Transcription factor GATA2 plays critical roles in hematopoietic stem cell survival and proliferation, GMP 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 <italic>Gata2</italic>
 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 <italic>Fcer1a</italic>
 mRNA and FcεRIα protein expression on both basophils and mast cells as well as for maintaining <italic>Kit</italic>
 mRNA and c-Kit protein expression on mast cells. GATA2 was required for histamine synthesis and was also critical for <italic>Il4</italic>
 mRNA expression in basophils and <italic>Il13</italic>
 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 <italic>Gata2</italic>
 gene. Overexpression of the <italic>Gata2</italic>
 gene was sufficient to direct basophil and mast cell differentiation in the absence of the <italic>Stat5</italic>
 gene. Our study reveals that the STAT5-GATA2 pathway is critical for basophil and mast cell differentiation and maintenance.</p>
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The STAT5-GATA2 Pathway Is Critical in Basophil and Mast Cell Differentiation and Maintenance

The STAT5-GATA2 Pathway Is Critical in Basophil and Mast Cell Differentiation and Maintenance

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Abstract

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