GATA-3 regulates the self-renewal of long-term hematopoietic stem cells

被引：84

作者：

Frelin, Catherine ^{[1
,2
]}

Herrington, Robert ^{[1
]}

Janmohamed, Salima ^{[3
]}

Barbara, Mary ^{[1
]}

Tran, Gary ^{[1
,2
]}

Paige, Christopher J. ^{[1
,2
,3
]}

Benveniste, Patricia ^{[3
,4
]}

Zuniga-Pfluecker, Juan-Carlos ^{[3
,4
]}

Souabni, Abdallah ^{[5
]}

Busslinger, Meinrad ^{[5
]}

Iscove, Norman N. ^{[1
,2
,3
,6
]}

机构：

[1] Univ Hlth Network, Ontario Canc Inst, Toronto, ON, Canada

[2] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[3] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[4] Sunnybrook Res Inst, Toronto, ON, Canada

[5] Res Inst Mol Pathol, A-1030 Vienna, Austria

[6] McEwen Ctr Regenerat Med, Toronto, ON, Canada

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 10期

基金：

加拿大健康研究院;

关键词：

P38; MAPK; PYRIMIDINYLIMIDAZOLE INHIBITORS; GENE-EXPRESSION; IN-VIVO; KINASE; CYTOKINE; DIFFERENTIATION; ALPHA; 5-FLUOROURACIL; AMPLIFICATION;

D O I：

10.1038/ni.2692

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The transcription factor GATA-3 is expressed and required for differentiation and function throughout the T lymphocyte lineage. Despite evidence it may also be expressed in multipotent hematopoietic stem cells (HSCs), any role for GATA-3 in these cells has remained unclear. Here we found GATA-3 was in the cytoplasm in quiescent long-term stem cells from steady-state bone marrow but relocated to the nucleus when HSCs cycled. Relocation depended on signaling via the mitogen-activated protein kinase p38 and was associated with a diminished capacity for long-term reconstitution after transfer into irradiated mice. Deletion of Gata3 enhanced the repopulating capacity and augmented the self-renewal of long-term HSCs in cell-autonomous fashion without affecting the cell cycle. Our observations position GATA-3 as a regulator of the balance between self-renewal and differentiation in HSCs that acts downstream of the p38 signaling pathway.

引用

页码：1037 / +

页数：10

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