GATA3 is redundant for maintenance and self-renewal of hematopoietic stem cells

被引:25
作者
Buza-Vidas, Natalija [1 ,2 ]
Duarte, Sara [1 ]
Luc, Sidinh [1 ]
Bouriez-Jones, Tiphaine [1 ]
Woll, Petter S. [1 ]
Jacobsen, Sten Eirik Waelgaard [1 ,3 ]
机构
[1] Univ Oxford, Haematopoiet Stem Cell Lab, Weatherall Inst Mol Med, John Radcliffe Hosp, Oxford OX3 9DS, England
[2] Univ Edinburgh, Inst Stem Cell Res, Edinburgh, Midlothian, Scotland
[3] Univ Oxford, MRC, Weatherall Inst Mol Med, John Radcliffe Hosp,Mol Haematol Unit, Oxford OX3 9DS, England
基金
英国医学研究理事会; 欧盟第七框架计划;
关键词
TRANSCRIPTION FACTOR GATA-3; LINEAGE COMMITMENT; GENE-EXPRESSION; IN-VIVO; DIFFERENTIATION; PROGENITORS; ONTOGENY; DELETION; RESCUE; LOCUS;
D O I
10.1182/blood-2011-02-338046
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
GATA3 has been identified as a master regulator of T helper cells, as well as being important for early thymic progenitors and T-cell commitment. However, Gata3 expression initiates already at the hematopoietic stem cell (HSC) level, implicating a potential role also in the regulation of HSCs. Herein we used a conditional Gata3 knockout strategy in which Gata3 expression was completely deleted from the earliest stage of embryonic hematopoietic development after emergence of HSCs from hemogenic endothelium. Through a detailed analysis of HSCs at the phenotypic and functional level, we demonstrate that steady-state levels of HSCs are normal in Gata3(fl/fl)Vav-Cre(tg/+) mice. Moreover, through long-term primary and secondary transplantation experiments, we also unequivocally demonstrate that Gata3 has a redundant role in post-transplantation HSC self-renewal. (Blood. 2011; 118(5):1291-1293)
引用
收藏
页码:1291 / 1293
页数:3
相关论文
共 24 条
[1]
Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential:: A revised road map for adult blood lineage commitment [J].
Adolfsson, J ;
Månsson, R ;
Buza-Vidas, N ;
Hultquist, A ;
Liuba, K ;
Jensen, CT ;
Bryder, D ;
Yang, LP ;
Borge, OJ ;
Thoren, LAM ;
Anderson, K ;
Sitnicka, E ;
Sasaki, Y ;
Sigvardsson, M ;
Jacobsen, SEW .
CELL, 2005, 121 (02) :295-306
[2]
Intermediate-Term Hematopoietic Stem Cells with Extended but Time-Limited Reconstitution Potential [J].
Benveniste, Patricia ;
Frelin, Catherine ;
Janmohamed, Salima ;
Barbara, Mary ;
Herrington, Robert ;
Hyam, Deborah ;
Iscove, Norman N. .
CELL STEM CELL, 2010, 6 (01) :48-58
[3]
Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter [J].
Chen, Michael J. ;
Yokomizo, Tomomasa ;
Zeigler, Brandon M. ;
Dzierzak, Elaine ;
Speck, Nancy A. .
NATURE, 2009, 457 (7231) :887-891
[4]
Transgenic mice with hematopoietic and lymphoid specific expression of Cre [J].
de Boer, J ;
Williams, A ;
Skavdis, G ;
Harker, N ;
Coles, M ;
Tolaini, M ;
Norton, T ;
Williams, K ;
Roderick, K ;
Potocnik, AJ ;
Kioussis, D .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (02) :314-325
[5]
Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1 [J].
Fujiwara, Y ;
Browne, CP ;
Cunniff, K ;
Goff, SC ;
Orkin, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (22) :12355-12358
[6]
From the cradle to the grave: activities of GATA-3 throughout T-cell development and differentiation [J].
Hosoya, Tomonori ;
Maillard, Ivan ;
Engel, James D. .
IMMUNOLOGICAL REVIEWS, 2010, 238 :110-125
[7]
GATA-3 is required for early T lineage progenitor development [J].
Hosoya, Tomonori ;
Kuroha, Takashi ;
Moriguchi, Takashi ;
Cummings, Dustin ;
Maillard, Ivan ;
Lim, Kim-Chew ;
Engel, James Douglas .
JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (13) :2987-3000
[8]
SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells [J].
Kiel, MJ ;
Yilmaz, ÖH ;
Iwashita, T ;
Yilmaz, OH ;
Terhorst, C ;
Morrison, SJ .
CELL, 2005, 121 (07) :1109-1121
[9]
Asymmetrical lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors [J].
Lai, Anne Y. ;
Kondo, Motonari .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (08) :1867-1873
[10]
GATA-2 plays two functionally distinct roles during the ontogeny of hematopoietic stem cells [J].
Ling, KW ;
Ottersbach, K ;
van Hamburg, JP ;
Oziemlak, A ;
Tsai, FY ;
Orkin, SH ;
Ploemacher, R ;
Hendricks, RW ;
Dzierzak, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (07) :871-882