Lineage tracing in the adult mouse corneal epithelium supports the limbal epithelial stem cell hypothesis with intermittent periods of stem cell quiescence

Natalie J. Dorà, Robert E. Hill, J. Martin Collinson, John D. West*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Citations (Scopus)
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Abstract

The limbal epithelial stem cell (LESC) hypothesis proposes that LESCs in the corneal limbus maintain the corneal epithelium both during normal homeostasis and wound repair. The alternative corneal epithelial stem cell (CESC) hypothesis proposes that LESCs are only involved in wound repair and CESCs in the corneal epithelium itself maintain the corneal epithelium during normal homeostasis. We used tamoxifen-inducible, CreER-. loxP lineage tracing to distinguish between these hypotheses. Clones of labelled cells were induced in adult CAGG-CreER;R26R-. LacZ reporter mice and their distributions analysed after different chase periods. Short-lived clones, derived from labelled transient amplifying cells, were shed during the chase period and long-lived clones, derived from stem cells, expanded. At 6. weeks, labelled clones appeared at the periphery, extended centripetally as radial stripes and a few reached the centre by 14. weeks. Stripe numbers depended on the age of tamoxifen treatment. Stripes varied in length, some were discontinuous, few reached the centre and almost half had one end at the limbus. Similar stripes extended across the cornea in CAGG-CreER;R26R-mT/mG reporter mice. The distributions of labelled clones are inconsistent with the CESC hypothesis and support the LESC hypothesis if LESCs cycle between phases of activity and quiescence, each lasting several weeks.

Original languageEnglish
Pages (from-to)665-677
Number of pages13
JournalStem Cell Research
Volume15
Issue number3
Early online date28 Oct 2015
DOIs
Publication statusPublished - 1 Nov 2015

Keywords

  • Cornea
  • Limbal epithelial stem cells
  • Limbus
  • Lineage tracing
  • Stem cell quiescence
  • Stem cells

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