In vitro Modeling of paraxial and lateral mesoderm differentiation reveals early reversibility
In vitro Modeling of paraxial and lateral mesoderm differentiation reveals early reversibility
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DOI：
10.1634/stemcells.2005-0256
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发表时间：
2006-03-01
期刊：
影响因子：
5.2
通讯作者：
Nishikawa, Shin-Ichi
中科院分区：
文献类型：
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作者：
Sakurai, Hidetoshi;Era, Takumi;Nishikawa, Shin-Ichi
内皮细胞被认为主要来源于胚胎发育早期的血管内皮生长因子受体2(VEGFR-2)(+)侧中胚层。在这项研究中，我们使用小鼠胚胎干细胞分化培养系统指定了几种EC分化的途径，该系统是早期胚胎发育过程中的细胞过程的模型。基于体外命运分析的结果，我们发现，在主要途径中，承诺的内皮细胞是通过VEGFR-2(+)血小板衍生生长因子受体α(PDGFR-α)(-)单阳性(VSP)群体分化而来的，该群体来自VEGFR-2(+)PDGFR-α(+)双阳性(DP)群体。DNA微阵列分析也证实了这一主要分化过程。然而，除了这一主要途径外，也可以从VEGFR-2-PDGFR-α(+)单阳性(PSP)群体产生ECs，PSP群体代表中轴旁中胚层血统，也来自DP群体。我们的结果有力地表明，即使在从共同的祖先DP群体分化为VSP和PSP群体后，这两个群体仍继续自发地转换其表面表型，从而导致最终命运的改变。VSP和PSP之间的这种谱系间转换的比率出人意料地高。由于这种经历命运转换的可能性，我们得出结论，在体外ES细胞分化过程中，ECs可以通过多条途径产生。
Endothelial cells (ECs) are thought to be derived mainly from the vascular endothelial growth factor receptor 2 (VEGFR-2)(+) lateral mesoderm during early embryogenesis. In this study, we specified several pathways for EC differentiation using a murine embryonic stem (ES) cell differentiation culture system that is a model for cellular processes during early embryogenesis. Based on the results of in vitro fate analysis, we show that, in the main pathway, committed ECs are differentiated through the VEGFR-2(+) platelet-derived growth factor receptor alpha (PDGFR-alpha)(-) single-positive (VSP) population that is derived from the VEGFR-2(+)PDGFR-alpha(+) double-positive (DP) population. This major differentiation course was also confirmed using DNA microarray analysis. In addition to this main pathway, however, ECs also can be generated from the VEGFR-2-PDGFR-alpha(+) single-positive (PSP) population, which represents the paraxial mesodermal lineage and is also derived from the DP population. Our results strongly suggest that, even after differentiation from the common progenitor DP population into the VSP and PSP populations, these two populations continue spontaneous switching of their surface phenotype, which results in switching of their eventual fates. The rate of this interlineage conversion between VSP and PSP is unexpectedly high. Because of this potential to undergo fate switch, we conclude that ECs can be generated via multiple pathways in in vitro ES cell differentiation.