Chen Guibin, Ye Zhaohui, Yu Xiaobing, Zou Jizhong, Mali Prashant, Brodsky Robert A, Cheng Linzhao
Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell Stem Cell. 2008 Apr 10;2(4):345-55. doi: 10.1016/j.stem.2008.02.004.
Pluripotent human embryonic stem (hES) cells can differentiate into various cell types derived from the three embryonic germ layers and extraembryonic tissues such as trophoblasts. The mechanisms governing lineage choices of hES cells are largely unknown. Here, we report that we established two independent hES cell clones lacking a group of cell surface molecules, glycosyl-phosphatidyl-inositol-anchored proteins (GPI-APs). The GPI-AP deficiency in these two hES clones is due to the deficiency in the gene expression of PIG-A (phosphatidyl-inositol-glycan class A), which is required for the first step of GPI synthesis. GPI-AP-deficient hES cells were capable of forming embryoid bodies and initiating cell differentiation into the three embryonic germ layers. However, GPI-AP-deficient hES cells failed to form trophoblasts after differentiation induction by embryoid body formation or by adding exogenous BMP4. The defect in trophoblast formation was due to the lack of GPI-anchored BMP coreceptors, resulting in the impairment of full BMP4 signaling activation in the GPI-AP-deficient hES cells. These data reveal that GPI-AP-enhanced full activation of BMP signaling is required for human trophoblast formation.
多能性人类胚胎干细胞（hES细胞）可分化为源自三个胚胎胚层以及滋养层等胚外组织的各种细胞类型。hES细胞谱系选择的调控机制在很大程度上尚不清楚。在此，我们报告我们建立了两个独立的hES细胞克隆，它们缺乏一组细胞表面分子，即糖基磷脂酰肌醇锚定蛋白（GPI-APs）。这两个hES克隆中GPI-AP的缺乏是由于PIG-A（磷脂酰肌醇聚糖A类）基因表达的缺陷，而PIG-A是GPI合成第一步所必需的。缺乏GPI-AP的hES细胞能够形成胚状体并启动细胞向三个胚胎胚层的分化。然而，通过胚状体形成或添加外源性BMP4进行分化诱导后，缺乏GPI-AP的hES细胞无法形成滋养层。滋养层形成缺陷是由于缺乏GPI锚定的BMP共受体，导致缺乏GPI-AP的hES细胞中BMP4信号的完全激活受损。这些数据表明，GPI-AP增强的BMP信号完全激活是人类滋养层形成所必需的。
