CD138/Syndecan-1 and SSEA-1 Mark Distinct Populations of Developing Ciliary Epithelium That Are Regulated Differentially by Wnt Signal

CD138/Syndecan-1 and SSEA-1 Mark Distinct Populations of Developing Ciliary Epithelium That Are Regulated Differentially by Wnt Signal
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DOI:
10.1634/stemcells.2008-0303
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发表时间:
2008-01-01
期刊:
影响因子:
5.2
通讯作者:
Watanabe, Sumiko
Watanabe, Sumiko
中科院分区:
医学2区
文献类型:
--
作者:
Koso, Hideto;Iida, Atsumi;Watanabe, Sumiko

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睫状体上皮(CE)由视泡发育而来,由非色素层和色素层组成。然而,CE发展的分子机制尚未得到密切的研究,部分原因是细胞表面标记物适合于特定的标记视网膜的亚区域是未知的。在这里,我们确定了CD 138/syndecan-1和阶段特异性胚胎抗原-1(SSEA-1)CD 15作为细胞表面抗原,分别标记无色素和色素CE。在视网膜发育过程中,CD 138和SSEA-1都在早期表达,这些标记物在组织中的分离开始于胚胎第10天左右。结果,在视网膜的最远端发现了CD 138阳性(CD 138+)细胞,并且在邻近CD 138表达区域的周边发现了SSEA-1+细胞。分离的CD 138+或SSEA-1+细胞亚群的体外表征显示,CD 138+细胞在E13和E16之间失去其视网膜祖细胞特征,表明它们在此期间致力于成为非色素CE细胞。通过小鼠体内模型,我们发现稳定的β-连环蛋白扩大了CD 138+非色素CE的面积,而β-连环蛋白的消除抑制了非色素CE细胞的发育。这些发现是第一次使用细胞表面标志物来确定在发展CE中发生的空间和时间转变。干细胞2008; 26:3162-3171
Ciliary epithelium (CE), which consists of nonpigmented and pigmented layers, develops from the optic vesicle. However, the molecular mechanisms underlying CE development have not been closely examined, in part because cell-surface markers suitable for specific labeling of subregions of the retina were unknown. Here, we identified CD138/syndecan-1 and stage specific embryonic antigen-1 (SSEA-1) CD15 as cell-surface antigens marking nonpigmented and pigmented CE, respectively. During retinal development, both CD138 and SSEA-1 were expressed in the early stage, and segregation of these markers in the tissue began at around embryonic day (E) 10. As a result, CD138-positive (CD138+) cells were found at the most distal tip of the retina, and SSEA-1+ cells were found in the periphery adjacent to the area of CD138 expression. In vitro characterization of isolated CD138+ or SSEA-1+ cell subpopulations revealed that CD138+ cells lose their retinal progenitor characteristics between E13 and E16, suggesting that they commit to becoming nonpigmented CE cells within this period. By in vivo mouse models, we found that stabilized beta-catenin expanded the area of CD138+ nonpigmented CE and that elimination of beta-catenin inhibited development of nonpigmented CE cells. These findings are the first to use cell-surface markers to ascertain the spatial and temporal transitions that occur in developing CE. STEM CELLS 2008; 26: 3162-3171