Stem Cell Unit, Department of Genetics, The Institute of Life Sciences, The Hebrew University, Edmund J. Safra Campus, Givat Ram, Jerusalem 91904, Israel.
Stem Cells. 2010 Jan;28(1):75-83. doi: 10.1002/stem.260.
Human embryoid bodies (HEBs) are cell aggregates that are produced during the course of embryonic stem cell differentiation in suspension. Mature HEBs have been shown to contain derivatives of the three embryonic germ layers. In this study, using a combination of laser capture microscopy followed by DNA microarray analysis and cell sorting, we demonstrate that early HEBs are composed of three major cell populations. These cell populations can be defined by the expression of specific cell markers, namely: (i) OCT4(+), REX1(-); (ii) NCAD(+), OCT4(-); and (iii) EPOR(+), OCT4(-). By analyzing gene expression in embryonic tissues, these cell populations could respectively be assigned to the embryonic ectoderm, mesendoderm, and extraembryonic endoderm lineages. We show that the extraembryonic endoderm, which selectively expresses platelet-derived growth factor B (PDGF-B), negatively affects the mesendoderm lineage, which selectively expresses the receptor PDGFRA. Our analysis suggests that early HEBs are spatially patterned and that cell differentiation is governed by interactions between the different cell types.
人胚体(HEBs)是在胚胎干细胞悬浮分化过程中产生的细胞聚集体。成熟的 HEBs 已被证明包含三个胚胎生殖层的衍生物。在这项研究中,我们使用激光捕获显微镜结合 DNA 微阵列分析和细胞分选,证明早期 HEBs 由三个主要细胞群组成。这些细胞群可以通过表达特定的细胞标记来定义,即:(i)OCT4(+),REX1(-); (ii)NCAD(+),OCT4(-); 和(iii)EPOR(+),OCT4(-)。通过分析胚胎组织中的基因表达,这些细胞群可以分别分配给胚胎外胚层、中胚层和胚胎外内胚层谱系。我们表明,选择性表达血小板衍生生长因子 B(PDGF-B)的胚胎外内胚层会对选择性表达受体 PDGFRA 的中胚层谱系产生负面影响。我们的分析表明,早期 HEBs 在空间上具有模式,细胞分化受不同细胞类型之间相互作用的控制。