Parp1-deficiency induces differentiation of ES cells into trophoblast derivatives
Parp1-deficiency induces differentiation of ES cells into trophoblast derivatives
复制标题
DOI：
10.1016/s0012-1606(03)00097-6
复制
发表时间：
2003-05-15
影响因子：
2.7
通讯作者：
Cross, JC
中科院分区：
文献类型：
--
作者：
Hemberger, M;Nozaki, T;Cross, JC
当将缺乏聚（ADP-核糖）聚合酶（Parp 1）的胚胎干（ES）细胞皮下注射到含有巨细胞样形态细胞的裸鼠体内时，会发展成畸胎瘤样肿瘤。我们在这里表明，这些细胞表达滋养层巨细胞的基因特征，因此属于滋养外胚层。脉此外，Parp 1（-/-）肿瘤包含其他滋养层亚型，如通过表达海绵滋养层特异性标记基因所揭示的。然而，与海绵滋养细胞相比，巨细胞分化的程度增强。在Parp 1缺陷的ES细胞培养物和Parp 1（-/-）胚胎的胎盘中观察到类似的向滋养层巨细胞分化的转变。对其他细胞谱系标记物的分析表明，Parp 1仅在滋养层中起作用以抑制分化。令人惊讶的是，滋养层衍生物也检测到野生型肿瘤和培养的ES细胞，虽然在显着较低的频率。这些数据表明，野生型ES细胞含有一小群具有滋养外胚层潜能的细胞，并且Parp 1的缺乏使ES细胞更容易采用滋养层表型。(C)2003 Elsevier Science（美国）。All rights reserved.
Embryonic stem (ES) cells deficient in the enzyme poly(ADP-ribose) polymerase (Parp1) develop into teratocarcinoma-like tumors when injected subcutaneously into nude mice that contain cells with giant cell-like morphology. We show here that these cells express genes characteristic of trophoblast giant cells and thus belong to the trophectoderm. lineage. In addition, Parp1(-/-) tumors contained other trophoblast subtypes as revealed by expression of spongiotrophoblast-specific marker genes. The extent of giant cell differentiation was enhanced, however, as compared with spongiotrophoblast. A similar shift toward trophoblast giant cell differentiation was observed in cultures of Parp1-deficient ES cells and in placentae of Parp1(-/-) embryos. Analysis of other cell lineage markers demonstrated that Parp1 acts exclusively in trophoblast to suppress differentiation. Surprisingly, trophoblast derivatives were also detected in wildtype tumors and cultured ES cells, albeit at significantly lower frequency. These data show that wildtype ES cells contain a small population of cells with trophectoderm potential and that absence of Parp1 renders ES cells more susceptible to adopting a trophoblast phenotype. (C) 2003 Elsevier Science (USA). All rights reserved.