GATA-3 promotes T-cell specification by repressing B-cell potential in pro-T cells in mice

被引：84

作者：

Garcia-Ojeda, Marcos E. ^{[1
,2
,3
]}

Wolterink, Roel G. J. Klein ^{[1
,2
,4
,5
]}

Lemaitre, Fabrice ^{[2
,6
]}

Richard-Le Goff, Odile ^{[1
,2
]}

Hasan, Milena ^{[1
,2
,7
]}

Hendriks, Rudolf W. ^{[4
]}

Cumano, Ana ^{[2
,3
]}

Di Santo, James P. ^{[1
,2
]}

机构：

[1] Inst Pasteur, Innate Immun Unit, F-75724 Paris, France

[2] INSERM, U668, Paris, France

[3] Inst Pasteur, Lymphocyte Dev Unit, Paris, France

[4] Erasmus MC, Dept Pulm Med, Rotterdam, Netherlands

[5] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France

[6] Inst Pasteur, Immune Response Dynam Unit, F-75724 Paris, France

[7] Inst Pasteur, Ctr Human Immunol, F-75724 Paris, France

来源：

BLOOD | 2013年 / 121卷 / 10期

关键词：

TRANSCRIPTION FACTOR GATA-3; NATURAL-KILLER-CELL; IFN-GAMMA PRODUCTION; DELTA-LIKE; 4; LINEAGE SPECIFICATION; ALPHA-BETA; NOTCH; DIFFERENTIATION; EXPRESSION; PROGENITORS;

D O I：

10.1182/blood-2012-06-440065

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Transcription factors orchestrate T-lineage differentiation in the thymus. One critical checkpoint involves Notch1 signaling that instructs T-cell commitment at the expense of the B-lineage program. While GATA-3 is required for T-cell specification, its mechanism of action is poorly understood. We show that GATA-3 works in concert with Notch1 to commit thymic progenitors to the T-cell lineage via 2 distinct pathways. First, GATA-3 orchestrates a transcriptional "repertoire" that is required for thymocyte maturation up to and beyond the pro-T-cell stage. Second, GATA-3 critically suppresses a latent B-cell potential in pro-T cells. As such, GATA-3 is essential to sealing in Notch-induced T-cell fate in early thymocyte precursors by promoting T-cell identity through the repression of alternative developmental options.

引用

页码：1749 / 1759

页数：11

共 51 条

[1]

The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer cell but no B-lymphocyte potential [J].