Hematopoietic lineage determination by transcription factors.

通过转录因子确定造血谱系。

• 批准号: 16590939
• 负责人: KITAJIMA Kenji
• 金额: $ 2.24万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590939/
• 关键词: Hematopoiesis; Differentiation; Embryonic stem cells; Transcription factor; Lineage switch; 血液; 赤血球; 巨核球; マクロファージ; クロマチン構造; 分子生物学

GATA-2 is a zinc finger transcription factor essential for differentiation of immature hematopoietic cells. We analyzed the function of GATA-2 by a combined method of tetracycline-dependent conditional gene expression and in vitro hematopoietic differentiation from mouse embryonic stem (ES) cells using OP9 stroma cells (OP9 system). In the presence of macrophage colony-stimulating factor (M-CSF), the OP9 system induced macrophage differentiation. GATA-2 expression in this system inhibited macrophage differentiation and redirected the fate of hematopoietic differentiation to other hematopoietic lineages. GATA-2 expression commencing at day 5 or day 6 induced megakaryocytic or erythroid differentiation, respectively. Expression levels of PU.1,a hematopoietic transcription factor that interferes with GATA-2,appeared to play a critical role in differentiation to megakaryocytic or erythroid lineages. Transcription of PU.1 was affected by histone acetylation induced by binding of GATA-2 to the PU.1 promoter region. This study demonstrates that the function of GATA-2 is modified in a contextdependent manner by expression of PU.1, which in turn is regulated by GATA-2.

加塔-2是一种锌指转录因子，对未成熟造血细胞的分化至关重要。我们通过四环素依赖的条件基因表达和使用OP 9基质细胞（OP 9系统）的小鼠胚胎干（ES）细胞体外造血分化的组合方法分析了加塔-2的功能。在巨噬细胞集落刺激因子（M-CSF）的存在下，OP 9系统诱导巨噬细胞分化。该系统中的加塔-2表达抑制巨噬细胞分化，并将造血分化的命运重定向到其他造血谱系。在第5天或第6天开始的加塔-2表达分别诱导巨核细胞或红细胞分化。PU. 1是一种干扰加塔-2的造血转录因子，其表达水平在向巨核细胞或红系分化中起关键作用。PU.1的转录受加塔-2与PU.1启动子区结合诱导的组蛋白乙酰化的影响。这项研究表明，加塔-2的功能是由PU.1的表达，这反过来又是由加塔-2调节的contextdependent方式修改。

项目成果

Cross Talk between Retinoic Acid Signaling and Transcription Factor GATA-2

• DOI: 10.1128/mcb.24.15.6824-6836.2004
• 发表时间: 2004-08
• 期刊: Molecular and Cellular Biology
• 影响因子: 5.3
• 作者: S. Tsuzuki;K. Kitajima;T. Nakano;A. Glasow;A. Zelent;T. Enver

Multpotential differentiation ability of GATA-1-null erythroid-committed cells.

GATA-1缺失的红系定型细胞的多向分化能力。

• 发表时间: 2006
• 期刊: Genes Dev 20
• 作者: Harada H;Suzu S;Hayashi Y;Okada S.;Zheng J;Kitajima K.
• 通讯作者: Kitajima K.

Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells

• DOI: 10.1182/blood-2005-04-1385
• 发表时间: 2006-01-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Zheng, J;Kitajima, K;Nakano, T
• 通讯作者: Nakano, T

Differentiation status dependent function of FOG‐1

• DOI: 10.1111/j.1365-2443.2004.00796.x
• 发表时间: 2004-12
• 期刊: Genes to Cells
• 影响因子: 2.1
• 作者: Makoto Tanaka;Jie Zheng;K. Kitajima;K. Kita;H. Yoshikawa;T. Nakano

Redirecting differentiation of hematopoietic progenitors by a transcription factor, GATA-2

• DOI: 10.1182/blood-2005-06-2527
• 发表时间: 2006-03-01
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Kitajima, K;Tanaka, M;Nakano, T
• 通讯作者: Nakano, T