Lancrin Christophe, Sroczynska Patrycja, Stephenson Catherine, Allen Terry, Kouskoff Valerie, Lacaud Georges
Cancer Research UK Stem Cell Biology Group.
Nature. 2009 Feb 12;457(7231):892-5. doi: 10.1038/nature07679. Epub 2009 Jan 28.
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 instead associates the first haematopoietic cells with a phenotypically differentiated endothelial cell that has haematopoietic potential (that is, a haemogenic endothelium). Support for the haemangioblast concept was initially provided by the identification during mouse embryonic stem cell 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 for 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 mouse embryos and generates haematopoietic cells on further culture. At the molecular level, we demonstrate that the transcription factor Tal1 (also known as Scl; ref. 10) is indispensable for the establishment of this haemogenic endothelium population whereas the core binding factor Runx1 (also known as AML1; ref. 11) is critical for generation of definitive haematopoietic cells from haemogenic endothelium. Together our results merge the two a priori conflicting theories on the origin of haematopoietic development into a single linear developmental process.
有人提出,在胚胎发育过程中,造血细胞起源于一种具有内皮和造血潜能的中胚层祖细胞,即成血管细胞。相反,一种与之矛盾的理论将最早的造血细胞与具有造血潜能的表型分化内皮细胞(即造血内皮)联系起来。对成血管细胞概念的支持最初来自于在小鼠胚胎干细胞分化过程中鉴定出的一种克隆前体,即胚泡集落形成细胞(BL-CFC),它能产生具有内皮和造血成分的胚泡集落。尽管最近的研究现已提供证据表明这种双能前体在体内存在,但从成血管细胞产生造血细胞的确切机制仍然完全未知。在这里,我们证明成血管细胞通过形成造血内皮中间体来产生造血细胞,这为这两个前体细胞群体之间提供了第一个直接联系。含有造血内皮的细胞群体在BL-CFC发育过程中短暂产生。这个细胞群体也存在于原肠胚形成期的小鼠胚胎中,并在进一步培养时产生造血细胞。在分子水平上,我们证明转录因子Tal1(也称为Scl;参考文献10)对于建立这个造血内皮细胞群体是必不可少的,而核心结合因子Runx1(也称为AML1;参考文献11)对于从造血内皮产生定型造血细胞至关重要。我们的结果共同将关于造血发育起源的两个先验矛盾的理论合并为一个单一的线性发育过程。