GATA-2 regulates granulocyte-macrophage progenitor cell function

被引：75

作者：

Rodrigues, Neil P. ^{[1
]}

Boyd, Ashleigh S. ^{[1
]}

Fugazza, Cristina ^{[1
]}

May, Gillian E. ^{[1
]}

Guo, YanPing ^{[1
]}

Tipping, Alex J.

Scadden, David T. ^{[2
,3
]}

Vyas, Paresh ^{[1
]}

Enver, Tariq ^{[1
]}

机构：

[1] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC,Hematol Unit, Oxford OX3 9DS, England

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA

[3] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

来源：

BLOOD | 2008年 / 112卷 / 13期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1182/blood-2008-01-136564

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The zinc finger transcription factor GATA-2 has been implicated in the regulation of hematopoietic stem cells. Herein, we explored the role of GATA-2 as a candidate regulator of the hematopoietic progenitor cell compartment. We showed that bone marrow from GATA-2 heterozygote (GATA-2(+/-)) mice displayed attenuated granulocyte-macrophage progenitor function in colony-forming cell (CFC) and serial replating CFC assays. This defect was mapped to the Lin(-)CD117(+)Sca-1(-)CD34(+)CD16/32(high) granulocyte-macrophage progenitor (GMP) compartment of GATA-2(+/-) marrow, which was reduced in size and functionally impaired in CFC assays and competitive transplantation. Similar functional impairments were obtained using a RNA interference approach to stably knockdown GATA-2 in wild-type GMP. Although apoptosis and cell-cycle distribution remained unperturbed in GATA-2(+/-) GMP, quiescent cells from GATA-2(+/-) GMP exhibited altered functionality. Gene expression analysis showed attenuated expression of HES-1 mRNA in GATA-2-deficient GMP. Binding of GATA-2 to the HES-1 locus was detected in the myeloid progenitor cell line 32Dcl3, and enforced expression of HES-1 expression in GATA-2(+/-) GMP rectified the functional defect, suggesting that GATA-2 regulates myeloid progenitor function through HES-1. These data collectively point to GATA-2 as a novel, pivotal determinant of GMP cell fate. (Blood. 2008;112:4862-4873)

引用

页码：4862 / 4873

页数：12

共 46 条

[31] Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates [J].