Rare corneal clones in mice suggest an age-related decrease of stem cell activity and support the limbal epithelial stem cell hypothesis
Rare corneal clones in mice suggest an age-related decrease of stem cell activity and support the limbal epithelial stem cell hypothesis
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DOI：
10.1016/j.scr.2011.08.007
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发表时间：
2012-01-01
影响因子：
1.2
通讯作者：
West, John D.
中科院分区：
文献类型：
--
作者：
Douvaras, Panagiotis;Webb, Sheila;West, John D.
前眼表面包括角膜、结膜和称为角膜缘的狭窄中间区域。人们普遍认为角膜上皮是由干细胞维持的，但不同的假设提出，在正常稳态期间维持小鼠角膜上皮的干细胞位于基底角膜缘上皮中或遍布基底角膜上皮。没有特定的标记来帮助测试这些替代品，需要新的方法来区分它们。我们观察到KRTLacZ/-转基因小鼠在角膜上皮中产生罕见的β-半乳糖苷酶（β-gal）阳性放射状条纹。这些条纹很可能是源自干细胞的细胞的克隆谱系，因此它们为活跃增殖的干细胞提供了谱系标记。 β-gal 阳性放射状条纹的分布表明它们从角膜缘向心延伸，支持角膜缘上皮干细胞（LESC）假说。条纹频率在 15 至 30 周之间下降，这预示干细胞功能会随着年龄的增长而下降。 Pax6(+/-)、KRT5(LacZ/-)角膜有小斑块而不是条纹，这证实了Pox6(+/-)小鼠的角膜维持异常。 (C) 2011 Elsevier B.V. 保留所有权利。
The anterior ocular surface comprises the cornea, conjunctiva and a narrow intermediate region called the limbus. It is widely accepted that the corneal epithelium is maintained by stem cells but different hypotheses propose that the stem cells that maintain the mouse corneal epithelium during normal homeostasis are located either in the basal limbal epithelium or throughout the basal corneal epithelium. There are no specific markers to help test these alternatives and new methods are required to distinguish between them. We observed that KRTLacZ/- transgenic mice produced rare beta-galactosidase (beta-gal)-positive radial stripes in the corneal epithelium. These stripes are likely to be clonal lineages of cells derived from stem cells, so they provide a lineage marker for actively proliferating stem cells. The distributions of the beta-gal-positive radial stripes suggested they extended centripetally from the limbus, supporting the limbal epithelial stem cell (LESC) hypothesis. Stripe frequency declined between 15 and 30 weeks, which predicts a reduction in stem cell function with age. Pax6(+/-), KRT5(LacZ/-) corneas had small patches rather than stripes, which confirms that corneal maintenance is abnormal in Pox6(+/-) mice. (C) 2011 Elsevier B.V. All rights reserved.