SCL interacts with VEGF to suppress apoptosis at the onset of hematopoiesis
SCL interacts with VEGF to suppress apoptosis at the onset of hematopoiesis
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DOI：
10.1242/dev.00968
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发表时间：
2004-02-01
期刊：
影响因子：
4.6
通讯作者：
Hoang, T
中科院分区：
文献类型：
--
作者：
Martin, R;Lahlil, R;Hoang, T
在发育过程中，卵黄囊内开始造血，这一过程依赖于VEGF/Flk1信号和SCL/Tal1转录因子的功能。我们发现VEGF改变了原始红系祖细胞的发育潜能，延长了它们的寿命。此外，卵黄囊红细胞在体内的存活取决于VEGF的剂量。有趣的是，在携带低变形等位基因的Vegf（lo/lo）胚胎中，flk1阳性细胞在E8.5时到达卵黄囊，但其产生原始红细胞前体的能力严重受损。这些观察结果表明，在胚胎发育过程中，造血前体细胞的迁移和克隆扩增需要不同的VEGF阈值。Vegf（lo/lo）胚胎中几乎没有原始红细胞前体与卵黄囊中低水平的Scl有关。引人注目的是，SCL的功能获得部分补充了由低变形的Vegf（lo/lo）等位基因引起的造血缺陷，并重建了红细胞的存活和红细胞基因（Gata1和betaH1）的表达。这表明SCL在VEGF的下游发挥作用，以确保造血室的扩张。
During development, hematopoiesis initiates in the yolk sac through a process that depends on VEGF/Flk1 signaling and on the function of the SCL/Tal1 transcription factor. Here we show that VEGF modifies the developmental potential of primitive erythroid progenitors and prolongs their life span. Furthermore, the survival of yolk sac erythrocytes in vivo depends on the dose of VEGF. Interestingly, in Vegf(lo/lo) embryos carrying a hypomorph allele, Flk1-positive cells reach the yolk sac at E8.5, but are severely compromised in their ability to generate primitive erythroid precursors. These observations indicate that during embryonic development, different thresholds of VEGF are required for the migration and clonal expansion of hematopoietic precursors. The near absence of primitive erythroid precursors in Vegf(lo/lo) embryos correlates with low levels of Scl in the yolk sac. Strikingly, gain-of-function of SCL partially complements the hematopoietic defect caused by the hypomorph Vegf(lo/lo) allele, and re-establishes the survival of erythroid cells and the expression of erythroid genes (Gata1 and betaH1). This indicates that SCL functions downstream of VEGF to ensure an expansion of the hematopoietic compartment.