Gata2 is required for HSC generation and survival.
Gata2 is required for HSC generation and survival.
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DOI：
10.1084/jem.20130751
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发表时间：
2013-12-16
期刊：
影响因子：
--
通讯作者：
Dzierzak E
中科院分区：
文献类型：
--
作者：
de Pater E;Kaimakis P;Vink CS;Yokomizo T;Yamada-Inagawa T;van der Linden R;Kartalaei PS;Camper SA;Speck N;Dzierzak E
GATA 2功能对于在内皮细胞向造血细胞转化阶段期间生成HSC以及此后对于HSC存活是必不可少的。驱动造血干细胞（HSC）生成的关键转录因子的知识对于当前的造血再生方法和重编程策略是特别重要的。尽管GATA 2长期以来被认为是造血转录因子，其表达失调与人类免疫缺陷综合征和血管完整性有关，但GATA 2在HSC生成中如何发挥作用尚不清楚。HSC由主要胚胎脉管系统（主动脉、卵黄动脉和脐动脉）的内皮细胞产生，并且在主动脉内造血簇中发现。在这项研究中，我们发现，GATA 2的功能是必不可少的造血干细胞的生成过程中的内皮细胞向造血细胞的过渡阶段。表达Vec（血管内皮钙粘蛋白）的内皮细胞中Gata2的特异性缺失导致缺乏长期再增殖的HSC和主动脉内簇细胞。通过在表达Vav的造血细胞中特异性缺失Gata2（在HSC生成后），我们进一步表明GATA 2对于HSC存活是必需的。这与RUNX1转录因子的已知活性形成对比，RUNX1转录因子仅在HSC的产生中起作用，并突出了在所有发育阶段对HSC中GATA 2功能的独特需求。
GATA2 function is essential for the generation of HSCs during the stage of endothelial-to-hematopoietic cell transition and thereafter for HSC survival Knowledge of the key transcription factors that drive hematopoietic stem cell (HSC) generation is of particular importance for current hematopoietic regenerative approaches and reprogramming strategies. Whereas GATA2 has long been implicated as a hematopoietic transcription factor and its dysregulated expression is associated with human immunodeficiency syndromes and vascular integrity, it is as yet unknown how GATA2 functions in the generation of HSCs. HSCs are generated from endothelial cells of the major embryonic vasculature (aorta, vitelline, and umbilical arteries) and are found in intra-aortic hematopoietic clusters. In this study, we find that GATA2 function is essential for the generation of HSCs during the stage of endothelial-to-hematopoietic cell transition. Specific deletion of Gata2 in Vec (Vascular Endothelial Cadherin)-expressing endothelial cells results in a deficiency of long-term repopulating HSCs and intra-aortic cluster cells. By specific deletion of Gata2 in Vav-expressing hematopoietic cells (after HSC generation), we further show that GATA2 is essential for HSC survival. This is in contrast to the known activity of the RUNX1 transcription factor, which functions only in the generation of HSCs, and highlights the unique requirement for GATA2 function in HSCs throughout all developmental stages.
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影响因子：
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作者：
Charles, Michael A.;Saunders, Thomas L.;Gordon, David F.
通讯作者：
Gordon, David F.
影响因子：
15.9
作者：
Johnson, Kirby D.;Hsu, Amy P.;Bresnick, Emery H.
通讯作者：
Bresnick, Emery H.
影响因子：
64.8
作者：
TSAI, FY;KELLER, G;ORKIN, SH
通讯作者：
ORKIN, SH
影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
DOI：
10.1084/jem.20031556
发表时间：
2004-10-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ling KW;Ottersbach K;van Hamburg JP;Oziemlak A;Tsai FY;Orkin SH;Ploemacher R;Hendriks RW;Dzierzak E
通讯作者：
Dzierzak E