Lacaud Georges, Kouskoff Valerie, Trumble Anne, Schwantz Staci, Keller Gordon
Carl C. Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Blood. 2004 Feb 1;103(3):886-9. doi: 10.1182/blood-2003-06-2149. Epub 2003 Oct 2.
The AML1 gene (recently renamed Runx1), which encodes the DNA-binding subunit of a transcription factor of the core binding factor (CBF) family, is required for the establishment of definitive hematopoiesis. We have previously demonstrated that Runx1 is expressed in yolk sac mesodermal cells prior to the establishment of the blood islands and in the embryoid body (EB)-derived blast-colony-forming cells (BL-CFCs), the in vitro equivalent of the hemangioblast. Analysis of Runx1-deficient embryonic stem (ES) cells demonstrated that this gene is essential for the generation of normal numbers of blast colonies, the progeny of the BL-CFCs. In the present study, we analyzed the potential of Runx1(+/-) ES cells to determine if heterozygosity at the Runx1 locus impacts early developmental events leading to the commitment of the BL-CFCs. Our results indicate that Runx1 heterozygosity leads to an acceleration of mesodermal commitment and specification to the BL-CFCs and to the hematopoietic lineages in EBs.
AML1基因（最近重新命名为Runx1）编码核心结合因子（CBF）家族转录因子的DNA结合亚基，是确定造血作用所必需的。我们之前已经证明，Runx1在血岛形成之前的卵黄囊间皮细胞以及胚状体（EB）来源的胚泡集落形成细胞（BL-CFC）中表达，BL-CFC是体外等效的成血管细胞。对Runx1缺陷型胚胎干细胞（ES细胞）的分析表明，该基因对于产生正常数量的胚泡集落（BL-CFC的后代）至关重要。在本研究中，我们分析了Runx1(+/-) ES细胞的潜能，以确定Runx1基因座的杂合性是否会影响导致BL-CFC定向分化的早期发育事件。我们的结果表明，Runx1杂合性会导致中胚层定向分化加速，并促使其向EB中的BL-CFC和造血谱系分化。
