Etv2 is expressed in the yolk sac hematopoietic and endothelial progenitors and regulates Lmo2 gene expression.
Etv2 is expressed in the yolk sac hematopoietic and endothelial progenitors and regulates Lmo2 gene expression.
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DOI：
10.1002/stem.1131
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发表时间：
2012-08
期刊：
影响因子：
5.2
通讯作者：
Garry, Daniel J.
中科院分区：
文献类型：
--
作者：
Koyano-Nakagawa, Naoko;Kweon, Junghun;Iacovino, Michelina;Shi, Xiaozhong;Rasmussen, Tara L.;Borges, Luciene;Zirbes, Katie M.;Li, Tongbin;Perlingeiro, Rita C. R.;Kyba, Michael;Garry, Daniel J.
在胚胎发生过程中，内皮细胞和造血细胞在卵黄囊的血岛原肠胚形成时首先出现。我们之前报道了Ets变异基因2 （Etv2/ER71）突变胚胎缺乏造血和内皮谱系，然而，Etv2在卵黄囊发育中的确切作用尚不清楚。在本研究中，我们利用Etv2突变体和一个新的Etv2- eyfp报告基因转基因系来确定Etv2在卵黄囊血岛发育中的作用。造血系和内皮系在Etv2突变的卵黄囊中都不存在。在Etv2-EYFP转基因小鼠中，EYFP报告基因在新生中胚层中被激活，在内皮细胞和血液祖细胞以及Tie2+、c-kit+、CD41+造血群体中表达。E7.75卵黄囊的造血活性仅局限于Etv2-EYFP+群体。在Etv2突变的卵黄囊中，存在Tie2+细胞，但不表达造血或内皮标志物。此外，这些细胞不会形成造血集落，这表明Etv2在造血谱系的规范中起着重要作用。在EB分化过程中，Etv2的强迫过表达诱导造血和内皮细胞谱系，在这种情况下，转录谱分析确定Lmo2是下游靶标。通过EMSA， ChIP，转录分析和诱变，我们证明了Etv2与Lmo2增强子结合并激活其表达。综上所述，我们的研究表明，Etv2在卵黄囊造血内皮发育过程中表达，并且是必需的，而Lmo2是Etv2的下游靶点之一。
During embryogenesis, the endothelial and the hematopoietic lineages first appear during gastrulation in the blood island of the yolk sac. We have previously reported that an Ets variant gene 2 (Etv2/ER71) mutant embryo lacks hematopoietic and endothelial lineages, however, the precise roles of Etv2 in yolk sac development remains unclear. In the present study, we define the role of Etv2 in yolk sac blood island development using the Etv2 mutant and a novel Etv2-EYFP reporter transgenic line. Both the hematopoietic and the endothelial lineages are absent in the Etv2 mutant yolk sac. In the Etv2-EYFP transgenic mouse, the EYFP reporter is activated in the nascent mesoderm, expressed in the endothelial and blood progenitors, and in the Tie2+, c-kit+, CD41+ hematopoietic population. The hematopoietic activity in the E7.75 yolk sac was exclusively localized to the Etv2-EYFP+ population. In the Etv2 mutant yolk sac, Tie2+ cells are present but do not express hematopoietic or endothelial markers. In addition, these cells do not form hematopoietic colonies, indicating an essential role of Etv2 in the specification of the hematopoietic lineage. Forced overexpression of Etv2 during EB differentiation induces the hematopoietic and the endothelial lineages, and transcriptional profiling in this context identifies Lmo2 as a downstream target. Using EMSA, ChIP, transcriptional assays and mutagenesis, we demonstrate that Etv2 binds to the Lmo2 enhancer and transactivates its expression. Collectively, our studies demonstrate that Etv2 is expressed during and required for yolk sac hemato-endothelial development, and that Lmo2 is one of the downstream targets of Etv2.
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影响因子：
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作者：
Li, WM;Ferkowicz, MJ;Yoder, MC
通讯作者：
Yoder, MC
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通讯作者：
Kyba, Michael