Integrins in slow-cycling corneal epithelial cells at the limbus in the mouse

Stem Cells. 2006 Apr;24(4):1075-86. doi: 10.1634/stemcells.2005-0382. Epub 2005 Nov 10.

Abstract

Adult corneal epithelial stem cells (CESCs) have been shown to reside at the periphery of the cornea at a site called the corneoscleral junction or limbus. Although studies have shown that these cells are slow cycling, their molecular characteristics are not well understood. Using a whole-mount procedure, we show that whereas alpha9-integrin is present in a subset of the basal cells at the corneal limbus and absent in the central cornea, beta1-, beta4-, alpha3-, and alpha6-integrins are more highly expressed overall in central corneal basal cells. To characterize CESCs based on their slow-cycling nature, we simultaneously evaluated 5-bromo-2-deoxyuridine (BrdU) label-retaining cells (LRCs) and integrin expression (alpha9, beta1, and beta4) in a total of 1,889 cells at the limbus of adult mice that had been injected as neonates with BrdU. Whereas the LRCs were usually observed adjacent to alpha9-integrin-positive cells, most LRCs were alpha9-integrin-negative and expressed high levels of beta1- and beta4-integrin. In addition, we observed more BrdU-positive LRCs at the superior and inferior quadrants of adult mouse corneas than at the nasal and temporal quadrants, and determined that 0.94 to 3.6% of the limbal basal cells were slow cycling. We conclude from these data that the slow-cycling LRCs in the adult mouse cornea are enriched in cells that express high levels of beta1- and beta4-integrin and little alpha9-integrin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Cycle
  • Epithelium, Corneal / cytology*
  • Epithelium, Corneal / metabolism*
  • Integrin alpha Chains / metabolism
  • Integrin alpha3 / metabolism
  • Integrin alpha6 / metabolism
  • Integrin beta1 / metabolism
  • Integrin beta4 / metabolism
  • Integrins / metabolism*
  • Limbus Corneae / cytology*
  • Limbus Corneae / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Models, Biological
  • Propidium
  • Stem Cells / cytology*
  • Stem Cells / metabolism*

Substances

  • Integrin alpha Chains
  • Integrin alpha3
  • Integrin alpha6
  • Integrin beta1
  • Integrin beta4
  • Integrins
  • integrin alpha9
  • Propidium
  • Bromodeoxyuridine