The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage.
The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage.
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DOI：
10.1038/nature07679
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发表时间：
2009-02-12
期刊：
影响因子：
64.8
通讯作者：
Lacaud, Georges
中科院分区：
文献类型：
--
作者：
Lancrin, Christophe;Sroczynska, Patrycja;Stephenson, Catherine;Allen, Terry;Kouskoff, Valerie;Lacaud, Georges
有人提出，在胚胎发育期间，造血细胞来自称为成血管细胞的具有内皮和造血潜能的中胚层祖细胞。相反，一种相互矛盾的理论将第一造血细胞与具有造血潜能的表型分化的内皮细胞（即造血内皮）相关联。对成血管细胞概念的支持最初是通过在胚胎干（ES）细胞分化过程中鉴定克隆前体--胚集落形成细胞（BL-CFC）来提供的，该细胞产生具有内皮和造血成分的胚集落。虽然最近的研究已经提供了证据证明这种双能前体在体内的存在，造血细胞从成血管细胞生成的确切机制仍然完全未知。在这里，我们证明了成血管细胞通过形成造血内皮中间体产生造血细胞，提供了这两个前体群体之间的第一个直接联系。在BL-CFC发育过程中瞬时产生含有造血内皮的细胞群。这种细胞群也存在于原肠胚中，并在进一步培养时产生造血细胞。在分子水平上，我们证明了转录因子Scl/Tal 1是建立造血内皮细胞群体所不可或缺的，而核心结合因子Runx 1/AML 1是造血内皮细胞生成永久造血细胞的关键。我们的结果合并成一个单一的线性发展过程中的两个先验相互冲突的理论起源的造血发展。
It has been proposed that during embryonic development haematopoietic cells arise from a mesodermal progenitor with both endothelial and haematopoietic potential called the haemangioblast. A conflicting theory associates instead the first haematopoietic cells with a phenotypically differentiated endothelial cell with haematopoietic potential, i.e. a haemogenic endothelium. Support for the haemangioblast concept was initially provided by the identification during embryonic stem (ES) cells differentiation of a clonal precursor, the blast colony-forming cell (BL-CFC), which gives rise to blast colonies with both endothelial and haematopoietic components. Although recent studies have now provided evidence for the presence of this bipotential precursor in vivo, the precise mechanism of generation of haematopoietic cells from the haemangioblast still remains completely unknown. Here we demonstrate that the haemangioblast generates haematopoietic cells through the formation of a haemogenic endothelium intermediate, providing the first direct link between these two precursor populations. The cell population containing the haemogenic endothelium is transiently generated during BL-CFC development. This cell population is also present in gastrulating embryos and generates haematopoietic cells upon further culture. At the molecular level, we demonstrate that the transcription factor Scl/Tal1 is indispensable for the establishment of this haemogenic endothelium population whereas the core binding factor Runx1/AML1 is critical for generation of definitive haematopoietic cells from haemogenic endothelium. Together our results merge into a single linear developmental process the two a priori conflicting theories on the origin of haematopoietic development.
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