RUNX1 and the endothelial origin of blood.

RUNX1 and the endothelial origin of blood.
复制标题

runx1和血液的内皮起源。

DOI:
10.1016/j.exphem.2018.10.009
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发表时间:
2018-12
影响因子:
2.6
通讯作者:
Speck NA
Speck NA
中科院分区:
医学4区
文献类型:
--
作者:
Gao L;Tober J;Gao P;Chen C;Tan K;Speck NA

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转录因子RUNX 1在胚胎中是形成成人造血系统所必需的。在这里,我们描述了导致发现RUNX 1及其在胚胎造血内皮细胞形成中的关键作用的开创性发现。我们还提供了RNA-Seq数据,证明不同解剖部位的生血内皮细胞(其产生具有不同分化潜能的造血祖细胞)在分子上是不同的。卵黄囊中的生血内皮细胞和非生血内皮细胞之间的关系比主要动脉中的生血内皮细胞和非生血内皮细胞之间的关系更密切。因此,与起源于大动脉的造血干细胞相比,卵黄囊中出现的定向红骨髓祖细胞的不同谱系潜能的主要驱动因素可能是它们所来源的生血内皮细胞的不同分子特性。我们使用生物信息学分析来预测动脉生血内皮细胞中的信号通路,其中包括功能验证的通路Notch、Wnt和Hedgehog。我们还使用了一种新的生物信息学方法来组装转录调控网络和预测转录因子,这些转录因子可能专门参与动脉生血内皮细胞的造血细胞形成,这是成人造血系统的起源。
The transcription factor RUNX1 is required in the embryo for formation of the adult hematopoietic system. Here we describe the seminal findings that led to the discovery of RUNX1 and of its critical role in blood cell formation in the embryo from hemogenic endothelium. We also present RNA-Seq data demonstrating that hemogenic endothelial cells in different anatomic sites, which produce hematopoietic progenitors with dissimilar differentiation potentials, are molecularly distinct. Hemogenic and non-hemogenic endothelial cells in the yolk sac are more closely related to each other than either are to hemogenic or non-hemogenic endothelial cells in the major arteries. Thus, a major driver of the different lineage potentials of the committed erythro-myeloid progenitors that emerge in the yolk sac, versus hematopoietic stem cells that originate in the major arteries, is likely to be the distinct molecular properties of the hemogenic endothelial cells from which they are derived. We use bioinformatics analyses to predict signaling pathways active in arterial hemogenic endothelium, which include the functionally validated pathways Notch, Wnt, and Hedgehog. We also use a novel bioinformatics approach to assemble transcriptional regulatory networks and predict transcription factors that may be specifically involved in hematopoietic cell formation from arterial hemogenic endothelium, which is the origin of the adult hematopoietic system.
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