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小鼠角膜上皮干细胞和祖细胞的谱系追踪

Lineage tracing of stem and progenitor cells of the murine corneal epithelium.

作者信息

Amitai-Lange Aya, Altshuler Anna, Bubley Jeffrey, Dbayat Noora, Tiosano Beatrice, Shalom-Feuerstein Ruby

机构信息

Department of Genetics and Developmental Biology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.

出版信息

Stem Cells. 2015 Jan;33(1):230-9. doi: 10.1002/stem.1840.

Abstract

Accumulating evidence supports the dogma that the corneal epithelium is regenerated by stem cells located exclusively in the limbal niche, at the corneal periphery. Accordingly, limbal stem cells (LSCs) give rise to progenitors that proliferate and migrate centripetally to repopulate the corneal epithelium, which has a short turnover. Moreover, LSC loss leads to corneal opacity and blindness, while limbal grafting restores patients' vision. However, contradicting data suggested that the limbus does not participate in corneal homeostasis and that the cornea contains stem cells. As of today, only indirect evidence for limbal cell migration under homeostasis or injury has been demonstrated. Here, we performed lineage tracing experiments using R26R-Confetti mice to follow K14+ limbal/corneal epithelial cells stochastically induced to express one out of four fluorescent genes. In homeostasis, radial limbal stripes of slow migrating cells proceeded toward the corneal center while, infrequently, slow cycling limbal clones resembling quiescent stem cells were observed. Additionally, rare corneal clones that did not migrate centripetally, but survived for over 4 months, were inspected. In contrast to limbal stripes, corneal clusters had minor contribution to tissue replenishment in homeostasis. Corneal cells, however, significantly contributed to mild wound repair while large limbal streaks appeared within a week following severe wounding that coincided with partial loss of corneal transparency. This data suggest that the mouse limbus largely contributes to corneal renewal while corneal progenitor cells have a long turnover and, therefore, may be able to maintain the corneal epithelium for several months.

摘要

越来越多的证据支持这样一种观点,即角膜上皮由仅位于角膜边缘角膜缘生态位的干细胞再生。因此,角膜缘干细胞(LSCs)产生祖细胞,这些祖细胞增殖并向心迁移以重新填充角膜上皮,角膜上皮的更新周期较短。此外,LSC缺失会导致角膜混浊和失明,而角膜缘移植可恢复患者视力。然而,相互矛盾的数据表明角膜缘不参与角膜内稳态,且角膜含有干细胞。截至目前,仅证明了在稳态或损伤情况下角膜缘细胞迁移的间接证据。在这里,我们使用R26R-Confetti小鼠进行谱系追踪实验,以追踪随机诱导表达四种荧光基因之一的K14 +角膜缘/角膜上皮细胞。在稳态下,缓慢迁移的细胞的放射状角膜缘条纹向角膜中心延伸,同时偶尔会观察到类似于静止干细胞的缓慢循环的角膜缘克隆。此外,还检查了罕见的不向心迁移但存活超过4个月的角膜克隆。与角膜缘条纹不同,角膜簇在稳态下对组织补充的贡献较小。然而,角膜细胞对轻度伤口修复有显著贡献,而在严重受伤后一周内出现大的角膜缘条纹,这与角膜透明度部分丧失同时发生。这些数据表明,小鼠角膜缘在很大程度上有助于角膜更新,而角膜祖细胞的更新周期较长,因此可能能够维持角膜上皮数月。

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