Cell cycle-dependent initiation and lineage-dependent abrogation of GATA-1 expression in pure differentiating hematopoietic progenitors.
Cell cycle-dependent initiation and lineage-dependent abrogation of GATA-1 expression in pure differentiating hematopoietic progenitors.
复制标题
纯分化造血祖细胞中 GATA-1 表达的细胞周期依赖性启动和谱系依赖性消除。
DOI：
10.1073/pnas.89.14.6353
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发表时间：
1992
影响因子：
11.1
通讯作者：
Orkin,SH
中科院分区：
文献类型：
--
作者：
Sposi,NM;Zon,LI;Carè,A;Valtieri,M;Testa,U;Gabbianelli,M;Mariani,G;Bottero,L;Mather,C;Orkin,SH
在早期造血分化中转录因子的程序性激活/抑制尚未被探索。DNA结合蛋白加塔-1是正常红细胞发育所必需的，并调节成熟成红细胞中红细胞表达的基因。我们分析了加塔-1在早期成人造血中的表达，通过使用体外系统，在该系统中，通过用造血生长因子进行差异化处理，选择性地沿着红细胞或粒细胞-巨噬细胞途径诱导“纯的”早期造血祖细胞逐渐和同步分化。加塔-1基因虽然在静止的祖细胞中几乎是沉默的，但在进入细胞周期后在造血生长因子刺激下被激活。随后，增加表达沿着红细胞途径与突然下调粒细胞-巨噬细胞谱系。这些结果提示分化造血祖细胞中加塔-1表达的微环境导向的两步模型，其涉及（i）周期依赖性起始和（ii）谱系依赖性维持或抑制。假设，开/关开关的谱系限制性反式激活因子可能是造血祖细胞的二元命运决定的基础。
The programmed activation/repression of transcription factors in early hematopoietic differentiation has not yet been explored. The DNA-binding protein GATA-1 is required for normal erythroid development and regulates erythroid-expressed genes in maturing erythroblasts. We analyzed GATA-1 expression in early human adult hematopoiesis by using an in vitro system in which "pure" early hematopoietic progenitors are induced to gradual and synchronized differentiation selectively along the erythroid or granulocyte-macrophage pathway by differential treatment with hematopoietic growth factors. The GATA-1 gene, though virtually silent in quiescent progenitors, is activated after entrance into the cell cycle upon stimulation with hematopoietic growth factors. Subsequently, increasing expression along the erythroid pathway contrasts with an abrupt downregulation in the granulocyte-macrophage lineage. These results suggest a microenvironment-directed, two-step model for GATA-1 expression in differentiating hematopoietic progenitors that involves (i) cycle-dependent initiation and (ii) lineage-dependent maintenance or suppression. Hypothetically, on/off switches of lineage-restricted transactivators may underlie the binary fate decisions of hematopoietic progenitors.