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ABCB5 is a limbal stem cell gene required for corneal development and repair.

Publication ,  Journal Article
Ksander, BR; Kolovou, PE; Wilson, BJ; Saab, KR; Guo, Q; Ma, J; McGuire, SP; Gregory, MS; Vincent, WJB; Perez, VL; Cruz-Guilloty, F; Kao, WWY ...
Published in: Nature
July 17, 2014

Corneal epithelial homeostasis and regeneration are sustained by limbal stem cells (LSCs), and LSC deficiency is a major cause of blindness worldwide. Transplantation is often the only therapeutic option available to patients with LSC deficiency. However, while transplant success depends foremost on LSC frequency within grafts, a gene allowing for prospective LSC enrichment has not been identified so far. Here we show that ATP-binding cassette, sub-family B, member 5 (ABCB5) marks LSCs and is required for LSC maintenance, corneal development and repair. Furthermore, we demonstrate that prospectively isolated human or murine ABCB5-positive LSCs possess the exclusive capacity to fully restore the cornea upon grafting to LSC-deficient mice in xenogeneic or syngeneic transplantation models. ABCB5 is preferentially expressed on label-retaining LSCs in mice and p63α-positive LSCs in humans. Consistent with these findings, ABCB5-positive LSC frequency is reduced in LSC-deficient patients. Abcb5 loss of function in Abcb5 knockout mice causes depletion of quiescent LSCs due to enhanced proliferation and apoptosis, and results in defective corneal differentiation and wound healing. Our results from gene knockout studies, LSC tracing and transplantation models, as well as phenotypic and functional analyses of human biopsy specimens, provide converging lines of evidence that ABCB5 identifies mammalian LSCs. Identification and prospective isolation of molecularly defined LSCs with essential functions in corneal development and repair has important implications for the treatment of corneal disease, particularly corneal blindness due to LSC deficiency.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

July 17, 2014

Volume

511

Issue

7509

Start / End Page

353 / 357

Location

England

Related Subject Headings

  • Wound Healing
  • Tumor Suppressor Proteins
  • Transcription Factors
  • Stem Cells
  • Stem Cell Transplantation
  • Regeneration
  • Molecular Sequence Data
  • Mice, Knockout
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ksander, B. R., Kolovou, P. E., Wilson, B. J., Saab, K. R., Guo, Q., Ma, J., … Frank, N. Y. (2014). ABCB5 is a limbal stem cell gene required for corneal development and repair. Nature, 511(7509), 353–357. https://doi.org/10.1038/nature13426
Ksander, Bruce R., Paraskevi E. Kolovou, Brian J. Wilson, Karim R. Saab, Qin Guo, Jie Ma, Sean P. McGuire, et al. “ABCB5 is a limbal stem cell gene required for corneal development and repair.Nature 511, no. 7509 (July 17, 2014): 353–57. https://doi.org/10.1038/nature13426.
Ksander BR, Kolovou PE, Wilson BJ, Saab KR, Guo Q, Ma J, et al. ABCB5 is a limbal stem cell gene required for corneal development and repair. Nature. 2014 Jul 17;511(7509):353–7.
Ksander, Bruce R., et al. “ABCB5 is a limbal stem cell gene required for corneal development and repair.Nature, vol. 511, no. 7509, July 2014, pp. 353–57. Pubmed, doi:10.1038/nature13426.
Ksander BR, Kolovou PE, Wilson BJ, Saab KR, Guo Q, Ma J, McGuire SP, Gregory MS, Vincent WJB, Perez VL, Cruz-Guilloty F, Kao WWY, Call MK, Tucker BA, Zhan Q, Murphy GF, Lathrop KL, Alt C, Mortensen LJ, Lin CP, Zieske JD, Frank MH, Frank NY. ABCB5 is a limbal stem cell gene required for corneal development and repair. Nature. 2014 Jul 17;511(7509):353–357.

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

July 17, 2014

Volume

511

Issue

7509

Start / End Page

353 / 357

Location

England

Related Subject Headings

  • Wound Healing
  • Tumor Suppressor Proteins
  • Transcription Factors
  • Stem Cells
  • Stem Cell Transplantation
  • Regeneration
  • Molecular Sequence Data
  • Mice, Knockout
  • Mice
  • Male