The "replacement hypothesis": corneal stem cell origin epithelia are replaced by limbal stem cell origin epithelia in mouse cornea during maturation.

The "replacement hypothesis": corneal stem cell origin epithelia are replaced by limbal stem cell origin epithelia in mouse cornea during maturation.
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DOI:
10.1097/ico.0b013e318269c83f
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发表时间:
2012-11-01
期刊:
影响因子:
2.8
通讯作者:
Ohashi, Yuichi
Ohashi, Yuichi
中科院分区:
医学3区
文献类型:
--
作者:
Hayashi, Yasuhito;Watanabe, Narumi;Ohashi, Yuichi

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目的:已有研究表明角膜上皮干细胞位于角膜缘基底层。角膜缘干细胞被认为是角膜上皮细胞增殖和分化的来源。方法:采用K12 IRES-Cre和Cre报告基因小鼠检测角膜上皮细胞角蛋白12的表达模式。2周龄后,向心K12 IRES-Cre表达逐渐从角膜缘区域延长。12周龄左右,角膜中央的马赛克表达模式消失。K12 IRES-Cre表达模式的时间和空间观察表明,镶嵌图案的细胞增殖,并聚集在同一位置,从胚胎期的15.5天最晚。结论:因此,这些细胞被认为是角膜干细胞起源上皮。相反,向心模式细胞群被认为是角膜缘干细胞来源的上皮细胞,因为它们起源于角膜缘区域并移动到角膜的中心。这些观察结果表明,在小鼠2周龄后,角膜干细胞来源的上皮细胞被角膜缘干细胞来源的上皮细胞取代。
PURPOSE: Previous studies have shown that the stem cells of corneal epithelia are located at the limbal basal layer. Limbal stem cells are believed to be the source of corneal epithelial cell proliferation and differentiation. This study tested the replacement hypothesis, which suggests that corneal stem cell origin epithelia may be replaced by limbal stem cell origin epithelia after 2 weeks of age in mice.METHODS: The cytokeratin 12 expression pattern in the cornea was examined using K12 IRES-Cre and Cre reporter mice.RESULTS: Before 2 weeks of age, K12 expression in corneal epithelia showed a mosaic pattern. After 2 weeks of age, centripetal K12 IRES-Cre expression gradually elongated from the limbal area. Around 12 weeks of age, the mosaic expression pattern disappeared from the center of the cornea. Temporal and spatial observations of K12 IRES-Cre expression patterns suggested that the mosaic pattern cells proliferated and amassed at the same position from day 15.5 of the embryonic stage at the latest.CONCLUSIONS: Therefore, these cells were considered corneal stem cell origin epithelia. In contrast, centripetal pattern cell populations were considered limbal stem cell origin epithelia because they originated from the limbal area and moved to the center of the cornea. These observations suggest that corneal stem cell origin epithelia are replaced by limbal stem cell origin epithelia after 2 weeks of age in mice.