Lineage Tracing of Stem and Progenitor Cells of the Murine Corneal Epithelium. (18th December 2014)

• Record Type: Journal Article
• Authors: Amitai-Lange, Aya; Altshuler, Anna; Bubley, Jeffrey; Dbayat, Noora; Tiosano, Beatrice; Shalom-Feuerstein, Ruby
• Is Part Of: Stem cells. Volume 33:Number 1(2015:Jan.)
• Page Start: 230
• Page End: 239
• Publication Date: 2014-12-18
• Subjects: Lineage tracing -- Limbal stem cells -- Stem cells -- Cornea -- Limbus; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1840
• Languages: English
• ISSNs: 1066-5099

Abstract

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. Stem Cells 2015;33:230–239