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

The loss of limbal stem cells (LSCs) due to injury or disease is one of the leading causes of blindness; here, the ABCB5 protein is identified as a marker of LSCs in mouse and human eye, and shown to be functionally required for LSC maintenance, corneal development and repair. ABCB5 gene in corneal development and repair The limbal stem cells (LSCs) in the basal limbal epithelium of the eye sustain corneal epithelial homeostasis and regeneration. Their loss due to injury or disease is one of the most common causes of blindness. Bruce Ksander et al . have now identified a marker — the ABC transporter ABCB5 — that is functionally required for LSC maintenance, corneal development and repair, and can be used to identify LSCs in mouse and human eyes. LSC transplantation experiments suggest that ABCB5-expressing cells could have potential in the treatment of corneal disease, particularly corneal blindness due to LSC deficiency. In a separate study in this issue of Nature , Hong Ouyang et al . establish a method for culturing LSCs in a feeder-free medium and demonstrate a role for the WNT7A–PAX6 signalling axis in specifying the corneal lineage, providing a possible therapeutic target in corneal surface diseases. Corneal epithelial homeostasis and regeneration are sustained by limbal stem cells (LSCs) 1 , 2 , 3 , and LSC deficiency is a major cause of blindness worldwide 4 . Transplantation is often the only therapeutic option available to patients with LSC deficiency. However, while transplant success depends foremost on LSC frequency within grafts 5 , a gene allowing for prospective LSC enrichment has not been identified so far 5 . Here we show that ATP-binding cassette, sub-family B, member 5 (ABCB5) 6 , 7 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 2 in mice and p63α-positive LSCs 8 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 a