Characterization of Gastrulation-Stage Progenitor Cells and Their Inhibitory Crosstalk in Human Embryoid Bodies
Characterization of Gastrulation-Stage Progenitor Cells and Their Inhibitory Crosstalk in Human Embryoid Bodies
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DOI：
10.1002/stem.260
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发表时间：
2010-01-01
期刊：
影响因子：
5.2
通讯作者：
Benvenisty, Nissim
中科院分区：
文献类型：
--
作者：
Kopper, Oded;Giladi, Odil;Benvenisty, Nissim
人胚状体（HEB）是胚胎干细胞在悬浮液中分化过程中产生的细胞聚集体。成熟的HEB已被证明含有三个胚层的衍生物。在这项研究中，使用激光捕获显微镜，然后DNA微阵列分析和细胞分选相结合，我们证明了早期HEBs是由三个主要的细胞群。这些细胞群可以通过特定细胞标志物的表达来定义，即：（i）0 CT 4（+）、REX 1 ㈠;（ii）NCAD（+）、0 CT 4 ㈠;和（iii）EPOR（+）、0 CT 4 ㈠。通过分析胚胎组织中的基因表达，这些细胞群可以分别归属于胚胎外胚层、中内胚层和胚外内胚层谱系。我们发现，选择性表达血小板衍生生长因子B（PDGF-B）的胚外内胚层对选择性表达受体PDGFRA的中内胚层谱系产生了负面影响。我们的分析表明，早期HEB的空间模式和细胞分化是由不同的细胞类型之间的相互作用。干细胞2010; 28：75-83
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. STEM CELLS 2010; 28: 75-83