Definitive hematopoiesis requires the mixed-lineage leukemia gene
Definitive hematopoiesis requires the mixed-lineage leukemia gene
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DOI：
10.1016/s1534-5807(04)00061-9
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发表时间：
2004-03-01
影响因子：
11.8
通讯作者：
Korsmeyer, SJ
中科院分区：
文献类型：
--
作者：
Ernst, P;Fisher, JK;Korsmeyer, SJ
混合谱系白血病（MLL）基因编码一个Trithorax相关的染色质修饰原癌基因，积极调节Hox基因。除了它们在轴向模式中的良好表征的作用之外，Trithorax和Polycomb家族蛋白在脊椎动物造血中执行较少理解的功能。为了确定MILL在造血系统发育中的作用，我们研究了缺乏MILL的细胞的潜力。在成年RAG-2嵌合动物中，MII缺陷细胞不能发育成淋巴细胞。类似地，B细胞的体外分化需要MLL。在嵌合体胚胎中，MII缺陷细胞未能促进胎肝造血干细胞/祖细胞群体。此外，我们发现来自MII缺陷胚胎的主动脉-性腺-中肾（AGM）细胞缺乏造血干细胞（HSC）活性，尽管它们能够在体外产生造血后代。这些结果证明了MILL在造血中的内在需求，其中MILL对于胚胎中HSC的产生是必需的。
The Mixed-Lineage Leukemia (MLL) gene encodes a Trithorax-related chromatin-modifying protooncogene that positively regulates Hox genes. In addition to their well-characterized roles in axial patterning, Trithorax and Polycomb family proteins perform less-understood functions in vertebrate hematopoiesis. To define the role of MILL in the development of the hematopoietic system, we examined the potential of cells lacking MILL. MII-deficient cells could not develop into lymphocytes in adult RAG-2 chimeric animals. Similarly, in vitro differentiation of B cells required MLL. In chimeric embryos, MII-deficient cells failed to contribute to fetal liver hematopoietic stem cell/progenitor populations. Moreover, we show that aorta-gonad-mesonephros (AGM) cells from MII-deficient embryos lacked hematopoietic stem cell [HSC) activity despite their ability to generate hematopoietic progeny in vitro. These results demonstrate an intrinsic requirement for MILL in definitive hematopoiesis, where it is essential for the generation of HSCs in the embryo.